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RNA virus
RNA virus
RNA virus
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Taxonomy and replication strategies of different types of RNA viruses

An RNA virus is a virus characterized by a ribonucleic acid (RNA) based genome.[1] The genome can be single-stranded RNA (ssRNA) or double-stranded (dsRNA).[2] Notable human diseases caused by RNA viruses include influenza, SARS, MERS, COVID-19, Dengue virus, hepatitis C, hepatitis E, West Nile fever, Ebola virus disease, rabies, polio, mumps, and measles.

All RNA viruses use a homologous RNA-dependent polymerase for replication and are categorized by the International Committee on Taxonomy of Viruses (ICTV) into the realm Riboviria.[3] This includes viruses belonging to Group III, Group IV, Group V, and Group VI of the Baltimore classification system. Group VI comprises the retroviruses, which have RNA genetic material but use DNA intermediates in their life cycle. Riboviria does not include viroids and satellite nucleic acids: Deltavirus, Avsunviroidae, and Pospiviroidae are taxa that were mistakenly included in 2019,[a] but this was corrected in 2020.[4]

Characteristics

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Single-stranded RNA viruses and RNA Sense

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RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense, or ambisense RNA viruses. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. Purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. In contrast, purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs. Ambisense RNA viruses resemble negative-sense RNA viruses, except they translate genes from their negative and positive strands.[5]

Double-stranded RNA viruses

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Further information: Double-stranded RNA viruses
Structure of the reovirus virion

The double-stranded (ds)RNA viruses represent a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi,[b] and bacteria), genome segment number (one to twelve), and virion organization (Triangulation number, capsid layers, spikes, turrets, etc.). Members of this group include the rotaviruses, which are the most common cause of gastroenteritis in young children, and picobirnaviruses, which are the most common virus in fecal samples of both humans and animals with or without signs of diarrhea. Bluetongue virus is an economically important pathogen that infects cattle and sheep. In recent years, progress has been made in determining atomic and subnanometer resolution structures of a number of key viral proteins and virion capsids of several dsRNA viruses, highlighting the significant parallels in the structure and replicative processes of many of these viruses.[2][page needed]

Mutation rates

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RNA viruses generally have very high mutation rates compared to DNA viruses,[7] because viral RNA polymerases lack the proofreading ability of DNA polymerases.[8] The genetic diversity of RNA viruses is one reason why it is difficult to make effective vaccines against them.[9] Retroviruses also have a high mutation rate even though their DNA intermediate integrates into the host genome (and is thus subject to host DNA proofreading once integrated), because errors during reverse transcription are embedded into both strands of DNA before integration.[10] Some genes of RNA virus are important to the viral replication cycles and mutations are not tolerated. For example, the region of the hepatitis C virus genome that encodes the core protein is highly conserved,[11] because it contains an RNA structure involved in an internal ribosome entry site.[12]

Sequence complexity

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On average, dsRNA viruses show a lower sequence redundancy relative to ssRNA viruses. Contrarily, dsDNA viruses contain the most redundant genome sequences while ssDNA viruses have the least.[13] The sequence complexity of viruses has been shown to be a key characteristic for accurate reference-free viral classification.[13]

Replication

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There are three distinct groups of RNA viruses depending on their genome and mode of replication:

  • Double-stranded RNA viruses (Group III) contain from one to a dozen different RNA molecules, each coding for one or more viral proteins.
  • Positive-sense ssRNA viruses (Group IV) have their genome directly utilized as mRNA, with host ribosomes translating it into a single protein that is modified by host and viral proteins to form the various proteins needed for replication. One of these includes RNA-dependent RNA polymerase (RNA replicase), which copies the viral RNA to form a double-stranded replicative form. In turn, this dsRNA directs the formation of new viral RNA.
  • Negative-sense ssRNA viruses (Group V) must have their genome copied by an RNA replicase to form positive-sense RNA. This means that the virus must bring along with it the enzyme RNA replicase. The positive-sense RNA molecule then acts as viral mRNA, which is translated into proteins by the host ribosomes.
  • Retroviruses (Group VI) have a single-stranded RNA genome but use DNA intermediates to replicate. Reverse transcriptase, a viral enzyme that comes from the virus itself after it is uncoated, converts the viral RNA into a complementary strand of DNA, which is copied to produce a double-stranded molecule of viral DNA. After this DNA is integrated into the host genome using the viral enzyme integrase, expression of the encoded genes may lead to the formation of new virions.

Recombination

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Numerous RNA viruses are capable of genetic recombination when at least two viral genomes are present in the same host cell.[14] Very rarely viral RNA can recombine with host RNA.[15] RNA recombination appears to be a major driving force in determining genome architecture and the course of viral evolution among Picornaviridae ((+)ssRNA), e.g. poliovirus.[16] In the Retroviridae ((+)ssRNA), e.g. HIV, damage in the RNA genome appears to be avoided during reverse transcription by strand switching, a form of recombination.[17][18][19] Recombination also occurs in the Reoviridae (dsRNA), e.g. reovirus; Orthomyxoviridae ((-)ssRNA), e.g. influenza virus;[19] and Coronaviridae ((+)ssRNA), e.g. SARS.[20] Recombination in RNA viruses appears to be an adaptation for coping with genome damage.[14] Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans.[20]

Classification

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Classification is based principally on the type of genome (double-stranded, negative- or positive-single-strand) and gene number and organization. Currently, there are 5 orders and 47 families of RNA viruses recognized. There are also many unassigned species and genera.

Related to but distinct from the RNA viruses are the viroids and the RNA satellite nucleic acids. These are not currently classified as RNA viruses and are described on their own pages.

A study of several thousand RNA viruses has shown the presence of at least five main taxa: a levivirus and relatives group; a picornavirus supergroup; an alphavirus supergroup plus a flavivirus supergroup; the dsRNA viruses; and the -ve strand viruses.[21] The lentivirus group appears to be basal to all the remaining RNA viruses. The next major division lies between the picornasupragroup and the remaining viruses. The dsRNA viruses appear to have evolved from a +ve RNA ancestor and the -ve RNA viruses from within the dsRNA viruses. The closest relation to the -ve stranded RNA viruses is the Reoviridae.

Positive-strand RNA viruses

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Main article: Positive-strand RNA virus

This is the single largest group of RNA viruses[22] and has been organized by the ICTV into the phyla Kitrinoviricota, Lenarviricota, and Pisuviricota in the kingdom Orthornavirae and realm Riboviria.[23]

Positive-strand RNA viruses can also be classified based on the RNA-dependent RNA polymerase. Three groups have been recognised:[24]

  1. Bymoviruses, comoviruses, nepoviruses, nodaviruses, picornaviruses, potyviruses, sobemoviruses and a subset of luteoviruses (beet western yellows virus and potato leafroll virus)—the picorna like group (Picornavirata).
  2. Carmoviruses, dianthoviruses, flaviviruses, pestiviruses, statoviruses, tombusviruses, single-stranded RNA bacteriophages, hepatitis C virus and a subset of luteoviruses (barley yellow dwarf virus)—the flavi like group (Flavivirata).
  3. Alphaviruses, carlaviruses, furoviruses, hordeiviruses, potexviruses, rubiviruses, tobraviruses, tricornaviruses, tymoviruses, apple chlorotic leaf spot virus, beet yellows virus and hepatitis E virus—the alpha like group (Rubivirata).

A division of the alpha-like (Sindbis-like) supergroup on the basis of a novel domain located near the N termini of the proteins involved in viral replication has been proposed.[25] The two groups proposed are: the 'altovirus' group (alphaviruses, furoviruses, hepatitis E virus, hordeiviruses, tobamoviruses, tobraviruses, tricornaviruses and probably rubiviruses); and the 'typovirus' group (apple chlorotic leaf spot virus, carlaviruses, potexviruses and tymoviruses).

The alpha like supergroup can be further divided into three clades: the rubi-like, tobamo-like, and tymo-like viruses.[26]

Additional work has identified five groups of positive-stranded RNA viruses containing four, three, three, three, and one order(s), respectively.[27] These fourteen orders contain 31 virus families (including 17 families of plant viruses) and 48 genera (including 30 genera of plant viruses). This analysis suggests that alphaviruses and flaviviruses can be separated into two families—the Togaviridae and Flaviridae, respectively—but suggests that other taxonomic assignments, such as the pestiviruses, hepatitis C virus, rubiviruses, hepatitis E virus, and arteriviruses, may be incorrect. The coronaviruses and toroviruses appear to be distinct families in distinct orders and not distinct genera of the same family as currently classified. The luteoviruses appear to be two families rather than one, and apple chlorotic leaf spot virus appears not to be a closterovirus but a new genus of the Potexviridae.

Evolution

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The evolution of the picornaviruses based on an analysis of their RNA polymerases and helicases appears to date to the divergence of eukaryotes.[28] Their putative ancestors include the bacterial group II retroelements, the family of HtrA proteases and DNA bacteriophages.

Partitiviruses are related to and may have evolved from a totivirus ancestor.[29]

Hypoviruses and barnaviruses appear to share an ancestry with the potyvirus and sobemovirus lineages respectively.[29]

Double-stranded RNA viruses

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This analysis also suggests that the dsRNA viruses are not closely related to each other but instead belong to four additional classes—Birnaviridae, Cystoviridae, Partitiviridae, and Reoviridae—and one additional order (Totiviridae) of one of the classes of positive ssRNA viruses in the same subphylum as the positive-strand RNA viruses.

One study has suggested that there are two large clades: One includes the families Caliciviridae, Flaviviridae, and Picornaviridae and a second that includes the families Alphatetraviridae, Birnaviridae, Cystoviridae, Nodaviridae, and Permutotretraviridae.[30]

Negative-strand RNA viruses

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Main article: Negative-strand RNA virus

These viruses have multiple types of genome ranging from a single RNA molecule up to eight segments. Despite their diversity it appears that they may have originated in arthropods and to have diversified from there.[31]

Satellite viruses

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A number of satellite viruses—viruses that require the assistance of another virus to complete their life cycle—are also known. Their taxonomy has yet to be settled. The following four genera have been proposed for positive sense single stranded RNA satellite viruses that infect plants—Albetovirus, Aumaivirus, Papanivirus and Virtovirus.[32] A family—Sarthroviridae which includes the genus Macronovirus—has been proposed for the positive sense single stranded RNA satellite viruses that infect arthropods.

Group III – dsRNA viruses

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Main article: Double-stranded RNA viruses

There are twelve families and a number of unassigned genera and species recognised in this group.[8]

Group IV – positive-sense ssRNA viruses

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Main article: Positive-sense single-stranded RNA virus

There are three orders and 34 families recognised in this group. In addition, there are a number of unclassified species and genera.

Satellite viruses

An unclassified astrovirus/hepevirus-like virus has also been described.[34]

Group V – negative-sense ssRNA viruses

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Main article: Negative-sense single-stranded RNA virus

This group of viruses has been placed into a single phylum—Negarnaviricota. This phylum has been divided into two subphyla—Haploviricotina and Polyploviricotina. Within the subphylum Haploviricotina four classes are currently recognised: Chunqiuviricetes, Milneviricetes, Monjiviricetes and Yunchangviricetes. In the subphylum Polyploviricotina two classes are recognised: Ellioviricetes and Insthoviricetes.

Six classes, eight orders, and thirty families are currently recognized in this group. A number of unassigned species and genera are yet to be classified.[8]

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See also

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Notes

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References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

RNA virus

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An RNA virus is a virus that has ribonucleic acid (RNA) as its genetic material and is capable of infecting a wide range of hosts, including humans, animals, , and , by replicating inside host cells using virally encoded enzymes. These viruses are distinguished from DNA viruses by their RNA genomes, which can be single-stranded (ssRNA) or double-stranded (dsRNA), linear or segmented, and range in size from approximately 3 to more than 40 kilobases. Unlike cellular organisms, RNA viruses lack the machinery for independent replication and must hijack host cellular processes, relying on an (RdRp) to synthesize their genomes and messenger RNAs. RNA viruses are classified primarily using the Baltimore classification system, which groups them based on genome type and mRNA synthesis strategy into four main categories: Group III (dsRNA viruses, such as reoviruses), Group IV (positive-sense ssRNA viruses, including picornaviruses and coronaviruses), Group V (negative-sense ssRNA viruses, like orthomyxoviruses and rhabdoviruses), and Group VI (positive-sense ssRNA viruses with reverse transcriptase, such as retroviruses). This system, established in 1971, highlights the diversity in replication mechanisms, with positive-sense RNA directly serving as mRNA for translation, while negative-sense RNA requires initial transcription into positive-sense intermediates. The International Committee on Taxonomy of Viruses (ICTV) further organizes RNA viruses into numerous families, such as Coronaviridae, Picornaviridae, Retroviridae, and Orthomyxoviridae, reflecting their morphological, genomic, and ecological differences. A defining feature of RNA viruses is their exceptionally high mutation rates, typically 10^{-3} to 10^{-5} errors per per replication cycle, driven by the error-prone nature of RdRp lacking activity. This genetic variability enables rapid evolution, quasispecies formation, and adaptation to new hosts or immune pressures, contributing to challenges in development and antiviral therapies. viruses account for a significant portion of emerging infectious diseases, with examples including viruses (), human immunodeficiency virus (Retroviridae), (), Ebola virus (), and severe acute respiratory syndrome coronavirus 2 (). Their ability to cause pandemics, such as the 1918 outbreak and the , underscores their public health impact, while also making them valuable models for studying and host-pathogen interactions.

Overview

Definition and Historical Discovery

RNA viruses are a diverse group of viruses that utilize ribonucleic acid (RNA) as their genetic material, in contrast to DNA viruses which employ deoxyribonucleic acid (DNA). Their genomes can be single-stranded (ssRNA) or double-stranded (dsRNA), and may exist as linear molecules or in segmented forms consisting of multiple RNA segments. Unlike most cellular organisms, RNA viruses lack the machinery for DNA synthesis and instead rely on RNA-dependent RNA polymerases encoded by their own genomes to replicate. This fundamental distinction places RNA viruses within the realm Riboviria in modern taxonomy, encompassing a wide array of pathogens that infect humans, animals, plants, and other organisms. The historical discovery of RNA viruses began in the late with investigations into plant diseases. In 1892, Russian microbiologist Dmitri Ivanovsky demonstrated that the causative agent of could pass through filters that retained bacteria, suggesting a submicroscopic infectious entity; this agent was later identified as the (TMV), the first recognized and a single-stranded virus. Building on this, Dutch microbiologist in 1898 coined the term "" to describe the filterable, non-bacterial pathogen of TMV, characterizing it as a "contagium vivum fluidum" (living infectious fluid) that multiplied only in living cells. These foundational observations marked the birth of , though the nature of the TMV was not yet known. Advancements in the confirmed the particulate nature and genetic composition of viruses. In the 1930s, the invention of the enabled the first visualizations of virus particles, including TMV in 1939 by and colleagues, providing direct evidence of their submicroscopic structure and distinguishing them from fluid-like agents. By the 1950s, biochemical analyses revealed the basis of animal virus genomes; notably, in 1955, researchers Frederick Schaffer and Carlton Schwerdt identified the genome of —a major —as single-stranded , solidifying RNA viruses as a distinct class. These discoveries shifted toward molecular understanding, highlighting RNA's role in . Early efforts to classify viruses laid the groundwork for systematic . In , André Lwoff, Robert Horne, and Paul Tournier proposed a foundational emphasizing viral properties like type, symmetry, and replication site, which first delineated viruses as a category. This was refined in 1971 by , who introduced a genome-based classification scheme grouping viruses by their type and mRNA synthesis method; viruses were divided into classes such as positive-sense ssRNA (e.g., TMV), negative-sense ssRNA, dsRNA, and reverse-transcribing viruses, providing a enduring framework for understanding viral diversity. Baltimore's remains central to virus today.

Biological and Medical Significance

RNA viruses play a pivotal role in due to their exceptionally high rates and genetic variability, which arise from error-prone RNA-dependent RNA polymerases, making them ideal models for studying rapid , , and in real time. This variability enables RNA viruses to serve as experimental systems for investigating fundamental processes like , recombination, and host-virus co-, providing insights into broader microbial and eukaryotic . Additionally, their diverse strategies for replication and , such as and ribosomal frameshifting, position RNA viruses as key models for understanding RNA processing, , and unconventional mechanisms of protein synthesis in cellular contexts. Medically, RNA viruses are major pathogens responsible for both acute respiratory illnesses and chronic infections, exemplified by viruses causing seasonal epidemics, human immunodeficiency virus () leading to acquired immunodeficiency syndrome (AIDS), and severe acute respiratory syndrome coronavirus 2 () triggering the . These viruses account for significant global morbidity and mortality, with alone resulting in hundreds of thousands of deaths annually and infecting 40.8 million [37.0 million–45.6 million] people worldwide as of 2024. Advances in countermeasures include vaccines like inactivated shots and live-attenuated options, as well as highly active antiretroviral therapy (HAART) for ; the crisis accelerated development, with platforms like those for demonstrating rapid deployment and high efficacy in eliciting immune responses. Antivirals such as for neuraminidase inhibition and for RNA polymerase blockade further highlight targeted therapies against RNA virus replication. The rapid evolutionary potential of RNA viruses poses substantial challenges, facilitating antigenic drift and shift that drive recurrent outbreaks and pandemics, as seen with influenza's ability to evade immunity through surface protein mutations. The 1918 H1N1 , caused by an RNA virus, resulted in an estimated 50 million deaths worldwide, underscoring their potential for catastrophic impact. Similarly, the , ongoing into 2025, has caused over 7 million confirmed deaths and economic losses exceeding $13 trillion globally, disrupting health systems and temporarily reversing a decade of progress in global while affecting billions through direct infections, lockdowns, and socioeconomic fallout. Beyond threats, RNA viruses have transformative research applications; the discovery of RNA interference (RNAi) stemmed from studies of plant virus infections, where double-stranded RNA from viruses triggers silencing of homologous sequences, revealing a conserved antiviral defense mechanism later harnessed for gene knockdown tools. In oncology, oncolytic RNA viruses like reoviruses and vesicular stomatitis virus are engineered for virotherapy, selectively replicating in and lysing tumor cells while stimulating antitumor immunity, with clinical trials showing promise for cancers such as melanoma and ovarian tumors.

Genomic Features

Types of RNA Genomes

RNA virus genomes exhibit structural diversity primarily in terms of strandedness and segmentation, which influence their packaging, transmission, and evolutionary dynamics. The majority of RNA viruses contain single-stranded (ssRNA) genomes, which can be either linear or, less commonly, circular. ssRNA genomes predominate across numerous viral families, such as Picornaviridae and for positive-sense linear forms, and represent the most common configuration among RNA viruses. In contrast, a notable exception is the hepatitis delta virus (HDV), which possesses a circular, negative-sense ssRNA genome of approximately 1.7 kb, enabling unique replication strategies akin to viroids. Double-stranded RNA (dsRNA) genomes are rarer among RNA viruses, occurring mainly in families like Reoviridae and Birnaviridae. These dsRNA genomes are typically linear and consist of multiple discrete segments, with Reoviridae viruses featuring 10 to 12 segments that encode structural and non-structural proteins. The segmented nature of dsRNA genomes facilitates selective packaging, where each segment is independently transcribed and packaged into virions. Segmentation is a key feature in both ssRNA and dsRNA viruses, with genomes divided into 1 to 12 independent RNA segments, though unsegmented (monopartite) forms are more prevalent in many ssRNA families. For instance, influenza viruses () have eight negative-sense ssRNA segments, allowing for efficient virion assembly and genetic exchange. This segmentation provides advantages in genome packaging by permitting the incorporation of specific segments via dedicated signals and enables reassortment during co-infection, which generates novel viral variants and contributes to rapid evolution. Overall, RNA virus genomes range in size from about 1.7 to over 40 kb, considerably smaller than those of many DNA viruses, which can exceed hundreds of kilobases. This size constraint arises from the error-prone nature of RNA-dependent RNA polymerases, which lack 3'–5' exonuclease proofreading activity, resulting in high mutation rates that limit genome expansion to prevent mutational meltdown.

Sense and Antisense Mechanisms

RNA viruses exhibit diverse genome polarities that determine their initial interactions with host cells, primarily categorized as positive-sense single-stranded RNA (+ssRNA), negative-sense single-stranded RNA (-ssRNA), and ambisense RNA. In positive-sense ssRNA viruses, the genomic has the same polarity and nucleotide sequence as (mRNA), allowing it to be directly recognized and translated by the host cell's ribosomes upon entry. This immediate translation produces viral proteins, including the (RdRp) necessary for subsequent genome replication, where the +ssRNA serves as a template to synthesize complementary negative-sense RNA intermediates. Representative examples include viruses from the Picornaviridae family, such as , and , like . Negative-sense ssRNA viruses possess genomic RNA that is complementary to mRNA, rendering it non-translatable by host machinery and necessitating the prior synthesis of positive-sense mRNAs for . To initiate , these viruses must package the RdRp within the virion, which uses the -ssRNA as a template to transcribe mRNAs directly in the shortly after entry. Examples include orthomyxoviruses, such as , and rhabdoviruses, like . Ambisense RNA viruses employ a hybrid strategy, where individual genome segments contain coding regions of both positive and negative polarities, requiring transcription from both the genomic RNA and its complementary strand to express all genes. This mixed approach is exemplified by arenaviruses, such as Lassa virus, in the family Arenaviridae, and certain viruses in the order Bunyavirales like virus (genus Phlebovirus, family Phenuiviridae), where the small (S) segment typically codes for in the negative sense and precursor in the positive sense. Like -ssRNA viruses, ambisense viruses package RdRp in the virion to enable initial transcription. These polarity mechanisms profoundly influence host-virus interactions: +ssRNA viruses benefit from a simpler entry process, leveraging the host's apparatus without needing pre-packaged enzymes, which facilitates rapid initial protein synthesis. In contrast, -ssRNA and ambisense viruses require virion-encapsidated RdRp for the first round of transcription, adding complexity to their lifecycle but enabling tight control over through nucleoprotein associations.

Virion Structure

Capsid and Genome Packaging

The of RNA viruses is a protein shell composed of self-assembling structural proteins known as capsomeres, which protect the enclosed and facilitate transmission between host cells. These capsids typically exhibit one of two primary symmetries: icosahedral, formed by 60 or multiples of 60 identical protein subunits arranged in a roughly spherical structure, or helical, where protein subunits and the wind around each other in a rod-like configuration. Icosahedral capsids are prevalent in many non-enveloped RNA viruses, providing efficient enclosure with minimal protein usage, while helical capsids accommodate elongated genomes by coiling the RNA along the protein lattice. Genome packaging within the capsid involves the selective incorporation of the viral , often guided by specific recognition motifs on the RNA molecule that interact with capsid proteins. In positive-sense single-stranded (+ssRNA) viruses, the RNA is typically coiled or folded inside the capsid, with packaging signals such as 5' cap structures or internal entry sites (IRES) in the untranslated regions facilitating specific binding and stabilization. These motifs ensure that only the full-length genomic RNA is encapsidated, excluding host or subgenomic RNAs, through electrostatic interactions between positively charged protein regions and the negatively charged RNA backbone. The process is highly specific, with capsid proteins often multimerizing around the RNA to drive spontaneous assembly. Icosahedral capsids typically have diameters of 20 to 100 nm, while helical capsids feature diameters of about 10 to 20 nm and lengths ranging from 100 nm to over 1,000 nm, depending on the length. Stability is conferred by inter-subunit bonds and the packaged itself, which can reinforce the structure; for instance, some non-enveloped virus capsids, such as those of enteroviruses, remain intact in acidic environments (pH 3-5), aiding survival in the . Non-enveloped viruses feature bare s exposed to the environment, enhancing resilience to detergents and , whereas enveloped viruses surround the with a derived from the host, providing additional protection but reducing overall stability.

Envelope and Surface Proteins

Many RNA viruses possess a lipid envelope surrounding their capsid and genome, which is derived from modified portions of the host cell's plasma membrane during the viral budding process. This envelope consists of a phospholipid bilayer incorporating host lipids and is studded with virus-encoded glycoproteins that project outward as spikes or peplomers. In contrast, non-enveloped RNA viruses, such as caliciviruses, lack this lipid layer and rely solely on their protein capsid for external protection. The surface embedded in the are critical for mediating interactions with host cells, primarily through receptor binding and fusion activities. These proteins are typically heavily glycosylated, with carbohydrate moieties aiding in proper folding, stability, and shielding from host immune responses. For instance, in viruses, the (HA) forms trimeric spikes that bind to residues on host cell surfaces, facilitating viral attachment. Similarly, the (GP) of virus serves dual roles in receptor engagement and low-pH-induced fusion of the viral and endosomal membranes. In flaviviruses, such as , E performs both attachment and fusion functions, highlighting the multifunctional nature of these surface proteins across enveloped RNA virus families. Glycosylation on these surface glycoproteins plays a key role in immune evasion by forming a glycan shield that masks underlying epitopes, reducing recognition by antibodies and reducing . This dense layer, often comprising up to 50% of the glycoprotein's mass in viruses like , sterically hinders access to conserved neutralization sites. Such modifications enable enveloped viruses to persist in host environments despite immune pressures, as observed in the surface proteins of coronaviruses and paramyxoviruses. While the provides an external barrier, it works in concert with the underlying to enclose and protect the viral .

Replication Cycle

Entry and Uncoating

The entry and uncoating of RNA viruses represent the initial critical phases of , enabling the viral genome to access the host cell's for subsequent replication. These processes involve specific interactions between viral surface proteins and host cell receptors, followed by internalization via or direct membrane fusion, and culminate in the disassembly of the virion to liberate the RNA genome. Most RNA viruses target the for replication, necessitating efficient uncoating mechanisms that respond to cellular cues such as pH changes or proteolytic processing. Attachment begins with the binding of viral envelope glycoproteins or capsid proteins to host cell surface receptors, a highly specific interaction that determines tissue tropism. For instance, influenza A viruses use hemagglutinin (HA) to bind sialic acid residues on glycoproteins or glycolipids, initiating receptor-mediated uptake. Similarly, SARS-CoV-2 employs its spike (S) protein to engage the angiotensin-converting enzyme 2 (ACE2) receptor on respiratory epithelial cells, often with assistance from co-receptors like neuropilin-1. In non-enveloped RNA viruses, such as picornaviruses (e.g., poliovirus or rhinovirus), capsid proteins like VP1 interact with receptors including CD155 or intercellular adhesion molecule 1 (ICAM-1), respectively. These binding events not only anchor the virus but also trigger signaling cascades that promote cytoskeletal rearrangements for efficient internalization. Entry into the host cell typically occurs through endocytosis, with clathrin-mediated endocytosis being a common route for many RNA viruses, though macropinocytosis or caveolar pathways are also utilized depending on the virus and cell type. For pH-dependent enveloped RNA viruses like influenza, the virion is trafficked to late endosomes where the acidic environment (pH ~5.0–6.0) induces conformational changes in HA, driving fusion of the viral envelope with the endosomal membrane and release of the viral ribonucleoprotein (vRNP) complex into the cytosol. Coronaviruses such as SARS-CoV-2 predominantly enter via endocytosis as well, but fusion can occur at the plasma membrane if the S protein is cleaved by surface proteases like TMPRSS2; otherwise, endosomal cathepsins (e.g., cathepsin L) process the protein in a pH-sensitive manner to trigger fusion. Non-enveloped RNA viruses, lacking an envelope for fusion, rely on endosomal acidification to initiate entry without membrane merger. Uncoating follows entry and involves the disassembly of the or complex to free the . In enveloped RNA viruses, fusion during entry effectively uncoats the by delivering it directly to the , often with additional cues like ubiquitination or dynein-mediated transport aiding vRNP dissociation; for , low endosomal and high concentrations further destabilize the M1 protein shell surrounding the vRNP. For non-enveloped picornaviruses, uncoating is triggered by low in late endosomes, causing irreversible expansion of the into an "A-particle" conformation; this exposes the of , which inserts into the endosomal to form a ~10 pore at the icosahedral two-fold symmetry axis, facilitating externalization and translocation of the positive-sense through the pore into the . These mechanisms ensure rapid release while minimizing exposure to host nucleases, highlighting the evolutionary adaptations of viruses to exploit host vesicular trafficking.

Genome Replication and Transcription

The (RdRp), also known as the RNA replicase, serves as the core for genome replication and transcription in RNA viruses of Baltimore Groups III, IV, and V, catalyzing the synthesis of RNA from an RNA template without requiring DNA intermediates. Unlike DNA polymerases, RdRp lacks 3' to 5' proofreading activity, rendering the replication process inherently error-prone and contributing to the high rates observed in RNA viruses. This is typically encoded within the viral and forms part of a replication-transcription complex (RTC) that associates with host cell membranes or cytoplasmic structures to shield viral RNA synthesis from innate immune detection. In positive-sense single-stranded RNA (+ssRNA) viruses, such as picornaviruses and flaviviruses, the genomic functions directly as mRNA upon entry into the host cell, undergoing to produce viral proteins including RdRp. Replication then proceeds in two main steps: first, the RdRp synthesizes a complementary negative-sense RNA (-RNA) strand using the +RNA genome as a template, forming a double-stranded RNA intermediate; subsequently, the -RNA serves as the template for producing new +RNA genomes and additional mRNAs. This process often occurs within virus-induced membrane-bound replication organelles that concentrate viral and host factors for efficient synthesis. For negative-sense single-stranded (-ssRNA) viruses, including orthomyxoviruses and paramyxoviruses, the genomic cannot serve as mRNA due to its antisense polarity; instead, the virion-associated RdRp initiates primary transcription immediately after uncoating, producing positive-sense mRNAs (+mRNA) from the - template within the ribonucleoprotein complex. Once sufficient viral proteins, including nucleoproteins, accumulate, replication shifts to full-length antigenome synthesis (+ complementary to the ), which then templates the production of new - progeny . This sequential transcription-replication switch is regulated by the availability of nucleoproteins and access to promoter sequences. Double-stranded RNA (dsRNA) viruses, such as reoviruses, package their RdRp within the virion core, enabling transcription of one strand of the dsRNA into +mRNA shortly after cell entry, without initial host . replication occurs conservatively in subviral particles—immature capsid-like structures—where parental dsRNA segments are transcribed into full-length +RNA intermediates that are then packaged with newly synthesized -RNA strands to form progeny dsRNA without mixing with host ribosomes. This enclosed mechanism ensures fidelity and segregation of viral segments during replication. Many RNA viruses with polycistronic , particularly +ssRNA viruses like coronaviruses, employ subgenomic RNAs (sgRNAs) to express downstream genes efficiently, avoiding the need for ribosomal frameshifting or polyprotein cleavage alone. In coronaviruses, sgRNAs are generated through discontinuous transcription, where the RdRp pauses at transcription-regulatory sequences (TRS) on the negative-sense template and switches to the 5' leader sequence of the , producing a nested set of 3'-coterminal mRNAs with common 5' and 3' ends. This strategy allows coordinated expression of structural and accessory proteins from a single promoter, with sgRNA abundance regulated by TRS strength and polymerase processivity. Reverse-transcribing RNA viruses of Group VI, such as retroviruses (e.g., human immunodeficiency virus), differ by using a DNA intermediate in their replication. Upon entry, the positive-sense ss genome is reverse-transcribed into double-stranded DNA by virion-packaged , an RNA-dependent . This proviral DNA is then integrated into the host cell genome by viral integrase, becoming a permanent . Host transcribes the provirus to produce full-length viral RNAs, which function as both mRNAs for translating viral proteins (via splicing for some) and as genomes packaged into new virions during assembly. This reliance on host transcription machinery and reverse transcription sets Group VI apart from other RNA viruses.

Genetic Variability

Mutation Rates and Error-Prone Polymerases

RNA viruses are characterized by exceptionally high mutation rates, typically ranging from 10^{-3} to 10^{-6} substitutions per per replication cycle, which is orders of magnitude higher than those observed in DNA-based organisms. This elevated variability stems primarily from their reliance on RNA-dependent RNA polymerases (RdRps), enzymes that synthesize RNA from RNA templates without the 3'–5' proofreading activity common in many DNA polymerases. As a result, errors introduced during replication accumulate rapidly, generating diverse viral populations known as quasispecies that enhance adaptability to host defenses and environmental pressures. The error-prone nature of RdRps is an inherent property of these viral enzymes, which prioritize replication speed over fidelity to support the rapid life cycles of RNA viruses. For instance, in , the 3D introduces approximately 10^{-4} mutations per copied, leading to about one per per replication cycle in its ~7.5 kb . Similarly, HIV-1's , an RNA-dependent DNA , exhibits a of around 10^{-5} substitutions per , compounded by frequent template switching. These rates reflect a evolutionary : while might reduce deleterious mutations, it could slow replication and impair fitness in dynamic host environments, as demonstrated by experiments where engineered higher-fidelity variants showed reduced despite lower loads. Not all RNA viruses conform to this pattern of extreme error proneness. Coronaviruses, such as , possess an accessory proofreading exonuclease (nsp14) that enhances RdRp fidelity, reducing the to approximately 10^{-6} per —about 10- to 15-fold lower than in proofreading-deficient relatives like murine hepatitis virus mutants. This mechanism allows for larger genome sizes (up to ~30 kb) without exceeding Eigen's error threshold, beyond which viral populations collapse due to excessive . Overall, the dynamics driven by these polymerases underpin the evolutionary success of RNA viruses, enabling rapid diversification while posing challenges for antiviral strategies that exploit their mutational vulnerability, such as lethal .

Recombination and Segment Reassortment

Recombination in RNA viruses involves the exchange of genetic material between viral genomes, primarily occurring through template switching by the viral (RdRp) during replication. This process, often termed copy-choice recombination, allows the polymerase to dissociate from one RNA template and associate with another, generating chimeric genomes. In positive-sense single-stranded RNA (+ssRNA) viruses, such as coronaviruses, this mechanism is frequent and facilitates adaptation by reshuffling genes, as seen in the evolution of variants through inter-genomic recombination in the spike gene. In contrast, recombination is rarer in negative-sense single-stranded RNA (-ssRNA) viruses due to the separation of replication and transcription compartments, though it can occur via similar template switching under co-infection conditions. Recombination mechanisms are classified as homologous or non-homologous, both driven by co-infection of the same host cell by two or more viral strains, which provides the necessary templates for exchange. Homologous recombination, the more common type, involves template switching at sites of high sequence similarity, preserving genome structure and often producing viable progeny, as exemplified in +ssRNA viruses like enteroviruses and coronaviruses. Non-homologous recombination, occurring without sequence homology, is less frequent and typically generates defective or rearranged genomes, potentially contributing to viral diversity but at lower efficiency. Recombination rates vary by virus but are estimated around 10^{-4} per site in susceptible +ssRNA viruses, exceeding baseline mutation rates and enabling rapid genetic diversification during mixed infections. Segment reassortment, a distinct form of genetic exchange unique to segmented RNA viruses, involves the packaging of genome segments from different parental viruses into a single virion during co-infection. This process shuffles entire segments without altering their sequences, leading to novel viral genotypes that can enhance transmissibility or host range. In influenza A viruses, which have eight negative-sense segments, reassortment drives antigenic shifts, as observed in the 2009 H1N1 pandemic where segments from human, avian, and swine strains combined. Rotaviruses, with 11 double-stranded segments, similarly undergo reassortment in the gut , contributing to strain diversity and vaccine escape, with frequencies reaching up to 10% of progeny in experimental mixed infections. Reassortment efficiency depends on segment compatibility and viral interference but is generally higher than recombination in non-segmented viruses due to independent segment packaging.

Classification

Baltimore Classification System

The Baltimore classification system, proposed by David Baltimore in 1971, categorizes viruses into seven groups based on their genomic nucleic acid type—whether DNA or RNA, single- or double-stranded, and sense (positive or negative)—and the specific pathway used to synthesize messenger RNA (mRNA) from the genome during replication. This framework emphasizes the central role of mRNA as the intermediary for protein synthesis, distinguishing viruses by how they bridge the gap between their genetic material and host translational machinery, such as through direct use of the genome as mRNA or reliance on viral polymerases for transcription or reverse transcription. Originally outlined for animal viruses, the system has since been broadly applied to all viruses, providing a functional rather than phylogenetic basis for organization. RNA viruses are assigned to groups III through VI within this scheme, reflecting their reliance on RNA-directed RNA polymerases (RdRps) or s for genome expression. Group III includes double-stranded RNA (dsRNA) viruses, which package segmented genomes and use virion-associated RdRp to transcribe one strand into mRNA. Group IV encompasses positive-sense single-stranded RNA (+ssRNA) viruses, whose non-segmented or segmented genomes function directly as mRNA upon entry into the host cell. Group V comprises negative-sense single-stranded RNA (-ssRNA) viruses, typically segmented, that carry RdRp in the virion to transcribe the genomic RNA into complementary mRNA. Group VI covers positive-sense ssRNA viruses that employ to generate a DNA from the RNA genome, which then serves as a template for mRNA production. These groupings underscore the diversity in RNA virus replication strategies while excluding DNA viruses (groups I, II, and VII). A primary advantage of the Baltimore system lies in its predictive power for viral replication mechanisms, enabling inferences about required enzymes, genome stability, and potential therapeutic targets without needing full genomic sequencing. It also integrates with the International Committee on Taxonomy of Viruses (ICTV) hierarchical taxonomy, where RNA virus groups III, IV, and V align with the realm Riboviria, a monophyletic assemblage defined by shared RdRp usage, thus bridging molecular function with evolutionary classification. Nonetheless, the system has notable limitations: it prioritizes replication pathways over phylogenetic relationships, host specificity, or ecological roles, and does not incorporate concepts like viral quasispecies dynamics that influence RNA virus evolution and adaptation.

Group III: Double-Stranded RNA Viruses

Group III viruses, also known as double-stranded RNA (dsRNA) viruses, are characterized by genomes consisting of segmented dsRNA molecules, typically packaged within non-enveloped, icosahedral capsids with multiple protein layers. These viruses replicate entirely in the host cell cytoplasm, utilizing viral RNA-dependent RNA polymerase (RdRp) enzymes packaged within the virion to initiate transcription without relying on host nuclear machinery. The genome segmentation, ranging from 2 to 12 linear dsRNA segments depending on the family, encodes structural proteins, polymerases, and non-structural factors essential for assembly and replication. The primary family within Group III is Reoviridae, which includes genera such as Orthoreovirus, , and Orbivirus, featuring 10–12 genome segments enclosed in a double-layered structure. Representative examples include rotaviruses, which infect mammals including humans, and bluetongue virus, which primarily affects ruminants. Another key family, Birnaviridae, possesses a bisegmented dsRNA (segments A and B) packaged in a single-shelled, non-enveloped icosahedral virion lacking the inner core typical of Reoviridae. Examples from this family, such as infectious bursal disease virus, target birds and aquatic animals. A smaller family, Picobirnaviridae, also features bisegmented genomes but remains less characterized. Replication of Group III viruses follows a conservative model, where the parental dsRNA duplex remains intact as a template for both transcription and replication within cytoplasmic subviral particles. Upon entry into the host cell via , the outer capsid layer is proteolytically removed to generate transcriptionally active cores, which contain the RdRp complex associated with each segment. The RdRp transcribes the negative-sense strand of each dsRNA segment into positive-sense mRNA, which exits the core through channels at the icosahedral vertices for into viral proteins in the . Subsequent replication within these cores synthesizes full-length complementary strands to form new dsRNA segments, packaged into progeny virions. The segmented nature of the facilitates genetic reassortment during co-infection, contributing to viral diversity. These viruses predominantly infect animals and , with Reoviridae spanning a broad host range including mammals, birds, , and , while Birnaviridae mainly affects vertebrates such as , amphibians, and . infections are rare and typically limited to specific Reoviridae members like certain rotaviruses.

Group IV: Positive-Sense Single-Stranded RNA Viruses

Group IV viruses possess a single-stranded RNA genome of positive polarity, which functions directly as (mRNA) and can be translated by host ribosomes to produce viral proteins immediately upon infection. This genomic feature distinguishes them from other RNA virus groups, enabling rapid initiation of the replication cycle without requiring prior transcription. sizes typically range from 3.5 to 40 kilobases, with most being non-segmented, though some exceptions exist. The viral encodes one or more large polyproteins that are proteolytically processed into structural and non-structural components, including the essential (RdRp). Unlike negative-sense viruses, Group IV virions do not package RdRp or other enzymes; these are synthesized de novo from the genomic . Replication occurs in the host cell , often on rearranged intracellular membranes, where the RdRp first generates a complementary negative-sense intermediate that serves as a template for producing new positive-sense genomic and, in certain families, subgenomic mRNAs for downstream open reading frames. Some members, like coronaviruses, employ mechanisms via a 3'-5' to maintain larger stability. Prominent families within Group IV include Picornaviridae, such as , which causes acute in humans through non-enveloped, icosahedral virions. Flaviviridae encompasses enveloped viruses like and , transmitted by vectors and leading to febrile illnesses in humans. Coronaviridae features enveloped pathogens including , which emerged as a major human respiratory threat. In plants, Potyviridae represents the largest family, with examples like infecting solanaceous crops and causing mosaic symptoms and yield losses. These viruses trace their origins to ancient RNA replicators, potentially from a primordial , as evidenced by the deep phylogenetic roots of their RdRp enzymes within the realm. Diversification is driven by high rates of approximately 10^{-3} to 10^{-5} substitutions per per replication cycle, owing to the error-prone nature of viral RdRp. Recombination serves as a key evolutionary mechanism, particularly in families like , where template-switching during replication creates hotspots in structural genes such as the , facilitating host jumps and variant emergence. Group IV viruses exhibit broad host , infecting organisms across multiple domains, including (e.g., Leviviridae in Enterobacteriaceae), fungi (e.g., Narnaviridae in yeasts), (e.g., Potyviridae in angiosperms), (e.g., Flaviviridae in mosquitoes), and vertebrates (e.g., Picornaviridae and in mammals). This versatility underscores their ecological significance and potential.

Group V: Negative-Sense Single-Stranded RNA Viruses

Group V viruses, also known as negative-sense single-stranded (-ssRNA) viruses, possess genomes that are complementary to (mRNA), rendering them incapable of direct translation by host ribosomes upon entry into a cell. Unlike positive-sense viruses, these genomes require transcription into positive-sense mRNA before protein synthesis can occur, a process mediated by a virion-packaged (RdRp). This polymerase, along with nucleoproteins, forms a ribonucleoprotein complex that protects the fragile genome and initiates primary transcription immediately after uncoating. Consequently, the purified genomic of -ssRNA viruses is non-infectious when introduced into cells, as it lacks the enzymatic machinery for transcription without the accompanying viral proteins. Key families within Group V include the , which encompass influenza viruses; the , including the ; the , such as the measles virus; the , featuring Ebola virus; and the Bunyaviridae (now reclassified into several families like Peribunyaviridae), which include viruses like La Crosse virus. These viruses are predominantly enveloped and exhibit diverse morphologies, from bullet-shaped (rhabdoviruses) to filamentous (filoviruses). Genome segmentation varies across families: most, such as those in and , have non-segmented genomes ranging from 10 to 19 kilobases, while genomes consist of eight distinct segments encoding up to 11 proteins in influenza A virus. Segmented -ssRNA viruses, including orthomyxoviruses and bunyaviruses, employ a unique cap-snatching mechanism, where the viral endonuclease cleaves 5' cap structures from host mRNAs to prime viral transcription, enhancing mRNA stability and translation efficiency.30321-X) -ssRNA viruses primarily infect vertebrates, causing significant diseases in humans, , and , with examples including respiratory infections from paramyxoviruses and hemorrhagic fevers from filoviruses. Certain families, notably Bunyaviridae, are arthropod-borne, utilizing mosquitoes, ticks, or sandflies as vectors that serve both as replicative hosts and transmission intermediaries to vertebrate hosts. In segmented viruses like , genome reassortment during co-infection can generate novel strains, contributing to and potential.

Group VI: Reverse-Transcribing RNA Viruses

Group VI viruses, also known as reverse-transcribing RNA viruses, are characterized by a positive-sense single-stranded (+ssRNA) genome that is replicated through a DNA intermediate, distinguishing them from other RNA viruses that directly use RNA-dependent RNA polymerases for replication. These viruses package two copies of their linear +ssRNA , typically 7–13 kb in length, as a dimer within enveloped virions. Upon entry into the host cell, the viral RNA serves as a template for reverse transcription, producing a double-stranded DNA (dsDNA) copy that integrates into the host . Central to their replication is the enzyme (RT), which possesses both and RNase H activities, enabling the synthesis of (cDNA) from the template while degrading the RNA strand in RNA-DNA hybrids. Reverse transcription begins in the using a host tRNA as a primer, generating a linear dsDNA molecule through a series of strand transfers and elongation steps. The resulting viral dsDNA is then processed by the viral integrase enzyme, which catalyzes its insertion into the host cell's chromosomal DNA, forming a that serves as a permanent template for viral . Integrase performs two key reactions: 3'-processing to expose reactive ends on the viral DNA and strand transfer to join these ends to the host DNA. The primary family in Group VI is Retroviridae, which includes subfamilies Orthoretrovirinae and , encompassing 11 genera without segmented genomes. Representative examples include human virus () from the genus and human T-lymphotropic virus (HTLV) from the Deltaretrovirus genus, both causing persistent infections in humans. The proviral integration enables a latent phase where the virus evades immune detection, with viral genes transcribed by host only upon cellular activation, leading to lifelong infection and potential oncogenesis or . Due to the error-prone nature of reverse transcriptase, lacking 3'–5' proofreading activity, these viruses exhibit high mutation rates, approximately 10^{-4} to 10^{-5} errors per , contributing to and immune evasion.

Evolution and Origins

Ancient Origins and Fossil Evidence

The evolutionary origins of RNA viruses are hypothesized to predate those of DNA viruses, consistent with the RNA world hypothesis, which proposes that self-replicating RNA molecules functioned as both genetic material and catalysts in primordial life, potentially including early RNA replicases that gave rise to viral polymerases. This scenario suggests RNA viruses emerged during an ancient phase of life dominated by -based biochemistry, before the transition to DNA genomes in cellular organisms. Although direct evidence for such early viruses is scarce due to RNA's instability, indirect genetic traces support their deep antiquity. Endogenous viral elements (EVEs)—genomic integrations of ancient viral sequences—serve as molecular fossils revealing past RNA virus infections. For instance, endogenous retroviral elements derived from reverse-transcribing viruses are widespread in mammalian genomes, with some integrations predating the divergence of placental mammals by over 100 million years. Similarly, bornavirus-like EVEs from negative-sense single-stranded viruses indicate infections exceeding 93 million years in s. In aquatic lineages, filovirus-like EVEs have been identified in fish genomes, suggesting RNA viruses infected early ancestors potentially hundreds of millions of years ago, based on host divergence timelines. Metagenomic analyses of environmental samples, particularly from , have uncovered a vast and diverse RNA virosphere, expanding known viral lineages and implying ancient origins tied to aquatic ecosystems. These studies reveal RNA viruses in and other microbes with phylogenetic depths reaching at least 600 million years, as seen in the order Articulavirales associated with early aquatic animals. Such findings highlight the as a cradle for RNA virus diversification, with enabling reconstruction of evolutionary histories far beyond traditional sampling. A key indicator of common ancestry among RNA viruses is the highly conserved (RdRp), an essential enzyme present across diverse groups from positive-sense to , tracing back to a shared primordial replicase. Evidence of , detected through metagenomic phylogenies, further underscores how ancient RNA viruses exchanged genetic material, contributing to their early radiation and adaptation.

Mechanisms of Diversification and Host Adaptation

RNA viruses exhibit exceptionally high rates, primarily due to the error-prone nature of their RNA-dependent RNA polymerases, which lack mechanisms, leading to frequent substitutions during replication. These rates, often exceeding 10^{-4} mutations per per replication cycle, generate a diverse array of genetic variants within a single infected host, forming what is known as a quasispecies—a dynamic population of closely related but non-identical genomes subjected to continuous variation, competition, and selection. This quasispecies structure enhances the virus's adaptability by providing a of mutants that can rapidly respond to selective pressures, such as immune responses or antiviral drugs. In addition to point mutations, recombination plays a crucial role in RNA virus diversification by allowing the exchange of genetic material between co-infecting viral genomes, producing chimeric variants with novel combinations of traits. This process is particularly prevalent in positive-sense single-stranded RNA viruses and segmented viruses, where it can accelerate the of new serotypes or enhance fitness in diverse environments. For instance, recombination contributes to the of coronaviruses, enabling the virus to explore broader and evade host defenses more effectively. Host adaptation in RNA viruses often occurs through spillover events, where viruses jump from reservoir species to new hosts, followed by rapid evolutionary changes that optimize transmission and replication in the novel environment. A prominent example is the 2019 emergence of , which likely spilled over from bats to humans via an intermediate host at a wildlife market in , , allowing the virus to adapt key mutations for efficient human ACE2 receptor binding. Similarly, highly pathogenic H5N1 has demonstrated repeated spillover from birds to mammals, including recent transmissions to in 2024, driven by mutations that alter receptor specificity and enhance mammalian cell tropism. Zoonotic reservoirs, primarily wildlife such as bats and birds, serve as the source for approximately 75% of emerging infectious diseases, providing a persistent pool from which RNA viruses can spill over to humans or other animals under conditions of increased contact, such as habitat encroachment. Climate change exacerbates these risks by expanding the geographic range and activity seasons of arthropod vectors like mosquitoes, which transmit RNA viruses such as dengue and West Nile, thereby facilitating more frequent spillover opportunities through altered vector-pathogen dynamics and extended transmission windows. Phylodynamic analyses, employing Bayesian statistical frameworks to integrate genetic sequences with epidemiological data, have been instrumental in quantifying RNA virus evolution rates and reconstructing adaptation timelines. For example, these models estimate the evolutionary rate of A viruses at approximately 10^{-3} substitutions per site per year, revealing how antigenic drift accumulates over seasons to drive host and vaccine escape. Such approaches highlight the interplay between , selection, and transmission in shaping viral diversification and .

Role in Disease and Ecology

Major Human Pathogens

RNA viruses are responsible for a wide array of significant human diseases, ranging from acute infections to chronic conditions and pandemics. Key families include Picornaviridae, , , and Retroviridae, among others, which collectively cause millions of cases annually and substantial mortality. These pathogens exploit diverse transmission routes and pose ongoing challenges due to their , which complicates development and therapeutic interventions. Picornaviruses, such as and , exemplify acute infections with fecal-oral transmission. , once a major cause of , has been nearly eradicated through global vaccination efforts, with only isolated wild poliovirus type 1 cases reported in and in 2025, totaling fewer than 100 confirmed instances. The inactivated and oral have reduced global incidence by over 99% since 1988, though vaccine-derived strains remain a concern in under-vaccinated areas. causes self-limiting liver , affecting an estimated 1.4 million people yearly worldwide, primarily in regions with poor , and is preventable by a highly effective administered in two doses. Flaviviruses like hepatitis C virus (HCV) lead to chronic liver disease through bloodborne transmission, often via shared needles or unsafe medical practices. Globally, an estimated 50 million people have chronic hepatitis C virus infection, with approximately 242,000 deaths in 2022 from related liver cirrhosis and hepatocellular carcinoma, though direct-acting antivirals achieve cure rates exceeding 95% in treated cases. Norovirus, from the Caliciviridae family, is the leading cause of viral gastroenteritis in humans, infecting about 685 million people annually and resulting in roughly 200,000 deaths, mainly in vulnerable populations; it spreads via fecal-oral route, contaminated food, or surfaces, with no specific vaccine available but hygiene measures reducing outbreaks by up to 50%. Coronaviruses, particularly , have caused unprecedented global impact through respiratory droplet transmission. The , declared in 2020, resulted in over 7 million confirmed deaths worldwide by mid-2025, though excess mortality estimates suggest higher figures due to underreporting. mRNA-based vaccines, such as those from Pfizer-BioNTech and , demonstrated 90-95% efficacy against severe disease in initial trials and have been administered to billions, though evolving variants like necessitate boosters to maintain protection above 70%. Influenza viruses (), also respiratory pathogens, cause seasonal epidemics and occasional pandemics; the 1918 H1N1 pandemic killed an estimated 50 million people, while the 2009 H1N1 outbreak affected over 60 million in the U.S. alone, with annual vaccines updated yearly to match circulating strains, reducing hospitalization by 40-60%. Retroviruses, notably from the Retroviridae family, establish lifelong infections via blood, sexual, or perinatal transmission, with 40.8 million people living with globally in 2024. Antiretroviral therapy suppresses to undetectable levels in over 29 million treated individuals, preventing progression to AIDS and reducing transmission by 96%, though no curative exists despite ongoing trials. These pathogens highlight the need for integrated strategies, including , , and antivirals, to mitigate their burden amid mutation-driven variants that evade immunity.

Impacts on Animals, Plants, and Ecosystems

RNA viruses exert profound effects on health, particularly through economically devastating diseases in and . , caused by a , is a highly contagious affecting cloven-hoofed animals such as , sheep, and pigs, leading to blisters, fever, and reduced productivity. Globally, it results in direct production losses and vaccination costs exceeding $21 billion annually in endemic regions. Similarly, , a , causes fatal neurological disease in a wide range of mammals, including dogs, , and , with outbreaks leading to significant culling and population declines in affected communities. While human fatalities from number approximately 59,000 per year, the virus inflicts even greater losses on populations through direct mortality and control measures. In plants, RNA viruses represent major agricultural threats, often lacking envelopes which facilitates their mechanical transmission via tools, sap, or . The (TMV), the first virus identified in plants in 1857, infects over 350 species including , tomatoes, and peppers, causing mottled leaves, stunted growth, and yield reductions. Potyviruses, the largest group of plant-infecting RNA viruses, affect crops like potatoes, beans, and cereals, with infections leading to mosaic symptoms, , and crop losses ranging from 10% to 53% depending on the host and strain. These viruses contribute to substantial global agricultural impacts, undermining in vulnerable regions. Beyond direct , RNA viruses play key ecological roles in regulating host populations and maintaining . By infecting and controlling microbial and animal communities, they influence primary productivity and biogeochemical cycles in terrestrial and aquatic ecosystems. Arboviruses, transmitted by vectors such as mosquitoes, exemplify this dynamic, as they modulate vector populations and host interactions, potentially preventing overpopulation of species and promoting through selective pressure. In marine environments, diverse viruses shape community structures, with their abundance correlating to and resilience. Many viruses bridge animal and human health via zoonotic transmission, underscoring their ecosystem-wide implications. Approximately 75% of emerging infectious diseases in humans originate from animal reservoirs, facilitating spillover events that disrupt dynamics. For instance, , carried by fruit bats, spills over to pigs and humans, causing severe outbreaks that affect bat populations indirectly through habitat changes and control efforts. Such zoonoses highlight how RNA viral circulation in animal hosts can destabilize ecosystems while posing risks to and conservation.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK8174/
  2. https://www.pnas.org/doi/10.1073/pnas.2501153122
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7173417/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC8483701/
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC7151951/
  6. https://pubmed.ncbi.nlm.nih.gov/9343347/
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC4763971/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC6157708/
  9. https://www.apsnet.org/edcenter/apsnetfeatures/Documents/1998/ZaitlinDiscoveryCausalAgentTobaccoMosaicVirus.pdf
  10. https://journals.sagepub.com/doi/10.1177/2096608321991292
  11. https://www.sciencedirect.com/topics/medicine-and-dentistry/tobacco-mosaic-virus
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC2772359/
  13. https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Introductory_Biology_%28CK-12%29/07%253A_Prokaryotes_and_Viruses/7.10%253A_Discovery_and_Origin_of_Viruses
  14. https://go.gale.com/ps/i.do?id=GALE%257CA15539705&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=00664197&p=AONE&sw=w
  15. https://www.sciencedirect.com/topics/immunology-and-microbiology/virus-classification
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC7157452/
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC34371/
  18. https://www.nature.com/articles/nrmicro863
  19. https://www.nature.com/articles/s41586-021-03511-5
  20. https://pmc.ncbi.nlm.nih.gov/articles/PMC12550694/
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC9201468/
  22. https://www.unaids.org/en/resources/fact-sheet
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC7114363/
  24. https://www.niaid.nih.gov/diseases-conditions/decades-making-mrna-covid-19-vaccines
  25. https://www.nature.com/articles/nrmicro.2017.118
  26. https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/1918-commemoration/1918-pandemic-history.htm
  27. https://www.who.int/news/item/24-05-2024-covid-19-eliminated-a-decade-of-progress-in-global-level-of-life-expectancy
  28. https://www.who.int/about/funding/invest-in-who/investment-case-2.0/challenges
  29. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01947-6/fulltext
  30. https://www.nature.com/articles/nature02874
  31. https://www.nature.com/articles/443906a
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC9779410/
  33. https://pmc.ncbi.nlm.nih.gov/articles/PMC4371325/
  34. https://www.nature.com/articles/323558a0
  35. https://www.pnas.org/doi/10.1073/pnas.1308649110
  36. https://pmc.ncbi.nlm.nih.gov/articles/PMC5119462/
  37. https://www.sciencedirect.com/topics/immunology-and-microbiology/genome-size
  38. https://www.pnas.org/doi/10.1073/pnas.2414223121
  39. https://pmc.ncbi.nlm.nih.gov/articles/PMC11388401/
  40. https://pmc.ncbi.nlm.nih.gov/articles/PMC7119911/
  41. https://pmc.ncbi.nlm.nih.gov/articles/PMC8474974/
  42. https://ictv.global/report/chapter/phenuiviridae
  43. https://pmc.ncbi.nlm.nih.gov/articles/PMC7173599/
  44. https://www.sciencedirect.com/topics/immunology-and-microbiology/virus-nucleocapsid
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC2948483/
  46. https://www.nature.com/articles/ncomms10113
  47. https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1198647/full
  48. https://pmc.ncbi.nlm.nih.gov/articles/PMC2771126/
  49. https://www.nature.com/articles/s41467-019-12341-z
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC7150055/
  51. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.638573/full
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC2829775/
  53. https://www.nature.com/articles/s41586-024-07899-8
  54. https://pubmed.ncbi.nlm.nih.gov/37994197/
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC7094621/
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC7169695/
  57. https://pmc.ncbi.nlm.nih.gov/articles/PMC3605244/
  58. https://pmc.ncbi.nlm.nih.gov/articles/PMC5407569/
  59. https://www.sciencedirect.com/science/article/pii/S0168952524000775
  60. https://www.sciencedirect.com/topics/immunology-and-microbiology/positive-strand-rna-virus
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC7169642/
  62. https://www.sciencedirect.com/topics/medicine-and-dentistry/negative-strand-rna-virus
  63. https://pubmed.ncbi.nlm.nih.gov/37137281/
  64. https://journals.asm.org/doi/10.1128/mmbr.00082-23
  65. https://pmc.ncbi.nlm.nih.gov/articles/PMC7158166/
  66. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000943
  67. https://www.pnas.org/doi/10.1073/pnas.1803885115
  68. https://pmc.ncbi.nlm.nih.gov/articles/PMC6025776/
  69. https://journals.asm.org/doi/abs/10.1128/jvi.01438-25
  70. https://www.embopress.org/doi/10.1093/emboj/cdf635
  71. https://www.ncbi.nlm.nih.gov/books/NBK190623/
  72. https://www.mdpi.com/1999-4915/13/9/1882
  73. https://journals.asm.org/doi/10.1128/jvi.01031-17
  74. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000003
  75. https://www.pnas.org/doi/10.1073/pnas.0501062102
  76. https://doi.org/10.1073/pnas.90.9.4171
  77. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00196-8
  78. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.870759/full
  79. https://www.nature.com/articles/nrmicro2614
  80. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003421
  81. https://doi.org/10.1016/B978-0-12-803109-4.00010-6
  82. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/double-stranded-rna-virus
  83. https://www.sciencedirect.com/topics/immunology-and-microbiology/birnaviridae
  84. https://pmc.ncbi.nlm.nih.gov/articles/PMC10218678/
  85. https://pmc.ncbi.nlm.nih.gov/articles/PMC7526681/
  86. https://pmc.ncbi.nlm.nih.gov/articles/PMC2908549/
  87. https://pmc.ncbi.nlm.nih.gov/articles/PMC6466366/
  88. https://pmc.ncbi.nlm.nih.gov/articles/PMC9866536/
  89. https://pmc.ncbi.nlm.nih.gov/articles/PMC7332303/
  90. https://pmc.ncbi.nlm.nih.gov/articles/PMC10632792/
  91. https://journals.asm.org/doi/10.1128/jvi.02274-20
  92. https://pmc.ncbi.nlm.nih.gov/articles/PMC10795101/
  93. https://pmc.ncbi.nlm.nih.gov/articles/PMC7150229/
  94. https://www.nature.com/articles/s41564-019-0513-7
  95. https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001712
  96. https://www.ncbi.nlm.nih.gov/books/NBK19383/
  97. https://pmc.ncbi.nlm.nih.gov/articles/PMC8671357/
  98. https://www.ncbi.nlm.nih.gov/books/NBK7934/
  99. https://pmc.ncbi.nlm.nih.gov/articles/PMC3185545/
  100. https://www.ncbi.nlm.nih.gov/books/NBK26876/
  101. https://pmc.ncbi.nlm.nih.gov/articles/PMC7609044/
  102. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02039/full
  103. https://www.sciencedirect.com/science/article/pii/S0042682215000549
  104. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011864
  105. https://pmc.ncbi.nlm.nih.gov/articles/PMC10636315/
  106. https://www.science.org/doi/10.1126/science.abm5847
  107. https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2017.00125/full
  108. https://pmc.ncbi.nlm.nih.gov/articles/PMC6282212/
  109. https://www.cell.com/trends/ecology-evolution/fulltext/S0169-5347%2808%2900055-4
  110. https://pmc.ncbi.nlm.nih.gov/articles/PMC2908548/
  111. https://wwwnc.cdc.gov/eid/article/4/4/98-0402_article
  112. https://pmc.ncbi.nlm.nih.gov/articles/PMC9158499/
  113. https://pmc.ncbi.nlm.nih.gov/articles/PMC3324781/
  114. https://academic.oup.com/gbe/article/14/12/evac161/6795266
  115. https://pmc.ncbi.nlm.nih.gov/articles/PMC2546865/
  116. https://www.nature.com/articles/s41579-021-00652-2
  117. https://www.nature.com/articles/s41586-024-07849-4
  118. https://www.cdc.gov/one-health/about/about-zoonotic-diseases.html
  119. https://www.cdc.gov/climate-health/php/effects/vectors.html
  120. https://pmc.ncbi.nlm.nih.gov/articles/PMC10151560/
  121. https://www.pnas.org/doi/10.1073/pnas.1916585116
  122. https://www.nature.com/articles/ncomms8952
  123. https://pmc.ncbi.nlm.nih.gov/articles/PMC5831953/
  124. https://www.who.int/news/item/28-07-2025-statement-of-the-forty-second-meeting-of-the-polio-ihr-emergency-committee
  125. https://www.who.int/health-topics/poliomyelitis
  126. https://www.who.int/news-room/fact-sheets/detail/hepatitis-a
  127. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
  128. https://www.cdc.gov/norovirus/about/index.html
  129. https://www.cdc.gov/norovirus/data-research/index.html
  130. https://data.who.int/dashboards/covid19/deaths
  131. https://www.who.int/publications/m/item/covid-19-epidemiological-update-edition-175
  132. https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/reconstruction-1918-virus.html
  133. https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/2009-h1n1-pandemic.html
  134. https://www.who.int/news-room/fact-sheets/detail/hiv-aids
  135. https://www.woah.org/en/disease/foot-and-mouth-disease/
  136. https://www.fao.org/newsroom/detail/fao-warns--enhanced-awareness-and-action-needed-amid-foot-and-mouth-disease-outbreaks-in-europe-and-the-near-east/en
  137. https://www.cfsph.iastate.edu/Factsheets/pdfs/rabies.pdf
  138. https://www.who.int/news-room/fact-sheets/detail/rabies
  139. https://nwdistrict.ifas.ufl.edu/hort/2020/04/15/the-virus-was-first-discovered-in-plants/
  140. https://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0185-33092025000100003&lng=pt&nrm=iso&tlng=en
  141. https://pmc.ncbi.nlm.nih.gov/articles/PMC7411817/
  142. https://link.springer.com/article/10.1007/s44370-025-00015-y
  143. https://pmc.ncbi.nlm.nih.gov/articles/PMC6351451/
  144. https://www.science.org/doi/10.1126/science.abn6358
  145. https://pmc.ncbi.nlm.nih.gov/articles/PMC9345211/
  146. https://www.sciencedirect.com/science/article/pii/S254251962200064X
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