Hubbry Logo
Bovine viral diarrheaBovine viral diarrheaMain
Open search
Bovine viral diarrhea
Community hub
Bovine viral diarrhea
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Contribute something
Bovine viral diarrhea
Bovine viral diarrhea
Bovine viral diarrhea
View on Wikipedia
from Wikipedia

Bovine viral diarrhea
Immunofluorescence image of BVDV (CP7 type) infected cells. Nuclei are stained blue with DAPI. The replication complexes of the viruses are marked red by NS3 protein binding antibodies
Immunofluorescence image of BVDV (CP7 type). Nuclei are stained blue with DAPI. The replication complexes of the viruses are marked red by NS3 protein binding antibodies
Scientific classificationEdit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order: Amarillovirales
Family: Flaviviridae
Genus: Pestivirus
Groups included
  • Pestivirus bovis (Bovine viral diarrhea virus 1)
  • Pestivirus tauri (Bovine viral diarrhea virus 2)
Cladistically included but traditionally excluded taxa
  • all other Pestivirus species
Tongue lesions on confirmed BVD/MD case (mucosal disease form)

Bovine viral diarrhea (BVD), bovine viral diarrhoea (UK English) or mucosal disease, previously referred to as bovine virus diarrhea (BVD), is an economically significant disease of cattle that is found in the majority of countries throughout the world.[1] Worldwide reviews of the economically assessed production losses and intervention programs (e.g. eradication programs, vaccination strategies and biosecurity measures) incurred by BVD infection have been published.[2][3] The causative agent, bovine viral diarrhea virus (BVDV), is a member of the genus Pestivirus of the family Flaviviridae.[1]

BVD infection results in a wide variety of clinical signs, due to its immunosuppressive effects,[4] as well as having a direct effect on respiratory disease and fertility.[5] In addition, BVD infection of a susceptible dam during a certain period of gestation can result in the production of a persistently infected (PI) fetus.[6]

PI animals recognise intra-cellular BVD viral particles as ‘self’ and shed virus in large quantities throughout life; they represent the cornerstone of the success of BVD as a disease.

Currently, it was shown in a worldwide review study that the PI prevalence at animal level ranged from low (≤0.8% Europe, North America, Australia), medium (>0.8% to 1.6% East Asia) to high (>1.6% West Asia). Countries that had failed to implement any BVDV control and/or eradication programmes (including vaccination) had the highest PI prevalence.[7]

Virus classification and structure

[edit]

BVDVs are members of the genus Pestivirus, belonging to the family Flaviviridae. Other members of this genus cause Border disease (sheep) and classical swine fever (pigs) which cause significant financial loss to the livestock industry.[8]

Pestiviruses are small, spherical, single-stranded, enveloped RNA viruses of 40 to 60 nm in diameter.[9]

The genome consists of a single, linear, positive-sense, single-stranded RNA molecule of approximately 12.3 kb.[10] RNA synthesis is catalyzed by the BVDV RNA-dependent RNA polymerase (RdRp). This RdRp can undergo template strand switching allowing RNA-RNA copy choice recombination during elongative RNA synthesis.[11]

Two BVDV genotypes are recognised, based on the nucleotide sequence of the 5’untranslated (UTR) region; BVDV-1 and BVDV-2.[12] BVDV-1 isolates have been grouped into 16 subtypes (a –p) and BVDV-2 has currently been grouped into 3 subtypes (a – c).[13]

BVDV strains can be further divided into distinct biotypes (cytopathic or non-cytopathic) according to their effects on tissue cell culture; cytopathic (cp) biotypes, formed via mutation of non-cytopathic (ncp) biotypes, induce apoptosis in cultured cells.[14] Ncp viruses can induce persistent infection in cells and have an intact NS2/3 protein. In cp viruses the NS2/3 protein is either cleaved to NS2 and NS3 or there is a duplication of viral RNA containing an additional NS3 region.[15] The majority of BVDV infections in the field are caused by the ncp biotype.[1]

Epidemiology

[edit]

BVD is considered one of the most significant infectious diseases in the livestock industry worldwide due to its high prevalence, persistence and clinical consequences.[16]

In Europe the prevalence of antibody positive animals in countries without systematic BVD control is between 60 and 80%.[17] Prevalence has been determined in individual countries and tends to be positively associated with stocking density of cattle.[18]

BVDV-1 strains are predominant in most parts of the world, whereas BVDV-2 represents 50% of cases in North America.[16] In Europe, BVDV-2 was first isolated in the UK in 2000 and currently represents up to 11% of BVD cases in Europe.[19]

Transmission of BVDV occurs both horizontally and vertically with both persistently and transiently infected animals excreting infectious virus. Virus is transmitted via direct contact, bodily secretions and contaminated fomites, with the virus being able to persist in the environment for more than two weeks. Persistently infected animals are the most important source of the virus, continuously excreting a viral load one thousand times that shed by acutely infected animals.[20]

Pathogenesis

[edit]
Turbinate cells infected with BVDV

Acute, transient infection

[edit]

Following viral entry and contact with the mucosal lining of the mouth or nose, replication occurs in epithelial cells. BVDV replication has a predilection for the palatine tonsils, lymphoid tissues and epithelium of the oropharynx.

Phagocytes take up BVDV or virus-infected cells and transport them to peripheral lymphoid tissues; the virus can also spread systemically through the bloodstream. Viraemia occurs 2–4 days after exposure and virus isolation from serum or leukocytes is generally possible between 3–10 days post infection.[21]

During systemic spread the virus is able to gain entry into most tissues with a preference for lymphoid tissues. Neutralising antibodies can be detected from 10 to 14 days post infection with titres continuing to increase slowly for 8–10 weeks. After 2–3 weeks, antibodies effectively neutralise viral particles, promote clearance of virus and prevent seeding of target organs.[22]

Intrauterine infections

[edit]

Fetal infection is of most consequence as this can result in the birth of a persistently infected neonate. The effects of fetal infection with BVDV are dependent upon the stage of gestation at which the dam suffers acute infection.

BVDV infection of the dam prior to conception, and during the first 18 days of gestation, results in delayed conception and an increased calving to conception interval. Once the embryo is attached, infection from days 29–41 can result in embryonic infection and resultant embryonic death.

Infection of the dam from approximately day 30 of gestation until day 120 can result in immunotolerance and the birth of calves persistently infected with the virus.

BVDV infection between 80 and 150 days of gestation may be teratogenic, with the type of birth defect dependent upon the stage of fetal development at infection. Abortion may occur at any time during gestation. Infection after approximately day 120 can result in the birth of a normal fetus which is BVD antigen-negative and BVD antibody-positive. This occurs because the fetal immune system has developed, by this stage of gestation, and has the ability to recognise and fight off the invading virus, producing anti-BVD antibodies.

Chronic infections

[edit]

BVD virus can be maintained as a chronic infection within some immunoprivileged sites following transient infection. These sites include ovarian follicles, testicular tissues, central nervous system and white blood cells. Cattle with chronic infections elicit a significant immune response, exhibited by extremely high antibody titres.

Clinical signs

[edit]

BVDV infection has a wide manifestation of clinical signs including fertility issues, milk drop, pyrexia, diarrhea, and fetal infection.[9] Occasionally, a severe acute form of BVD may occur. These outbreaks are characterized by thrombocytopenia with high morbidity and mortality. However, clinical signs are frequently mild and infection insidious, recognized only by BVDV's immunosuppressive effects perpetuating other circulating infectious diseases (particularly scours and pneumonias).

PI animals

[edit]

Persistently infected animals did not have a competent immune system at the time of BVDV transplacental infection. The virus, therefore, entered the fetal cells and, during immune system development, was accepted as self. In PIs the virus remains present in a large number of the animal's body cells throughout its life and is continuously shed. PIs are often ill-thrifty and smaller than their peers, however, they can appear normal. PIs are more susceptible to disease, with only 20% of PIs surviving to two years of age.[23] If a PI dam is able to reproduce they always give birth to PI calves.[24]

Mucosal disease

[edit]

The PI cattle that do survive ill-thrift are susceptible to mucosal disease. Mucosal disease only develops in PI animals and is invariably fatal.[5] Disease results when a PI animal is superinfected with a cytopathic biotype arising from mutation of the non-cytopathic strain of BVDV already circulating in that animal.[25] The cp BVDV spreads to the gastro-intestinal epithelium, and necrosis of keratinocytes results in erosion and ulceration. Fluid leaks from the epithelial surface of the gastro-intestinal tract causing diarrhoea and dehydration. In addition, bacterial infection of the damaged epithelium results in secondary septicaemia. Death occurs in the ensuing days or weeks.

Diagnosis

[edit]

Various diagnostic tests are available for the detection of either active infection or evidence of historical infection. The method of diagnosis used also depends upon whether the vet is investigating at an individual or a herd level.

Virus or antigen detection

[edit]

Antigen ELISA and rtPCR are currently the most frequently performed tests to detect virus or viral antigen. Individual testing of ear tissue tag samples or serum samples is performed. It is vital that repeat testing is performed on positive samples to distinguish between acute, transiently infected cattle and PIs. A second positive result, acquired at least three weeks after the primary result, indicates a PI animal. rtPCR can also be used on bulk tank milk (BTM) samples to detect any PI cows contributing to the tank. It is reported that the maximum number of contributing cows from which a PI can be detected is 300.

BVD antibody detection

[edit]

Antibody (Ig) ELISAs are used to detect historical BVDV infection; these tests have been validated in serum, milk and bulk milk samples. Ig ELISAs do not diagnose active infection but detect the presence of antibodies produced by the animal in response to viral infection. Vaccination also induces an antibody response, which can result in false positive results, therefore it is important to know the vaccination status of the herd or individual when interpreting results. A standard test to assess whether virus has been circulating recently is to perform an Ig ELISA on blood from 5–10 young stock that have not been vaccinated, aged between 9 and 18 months. A positive result indicates exposure to BVDV, but also that any positive animals are very unlikely to be PI animals themselves. A positive result in a pregnant female indicates that she has previously been either vaccinated or infected with BVDV and could possibly be carrying a PI fetus, so antigen testing of the newborn is vital to rule this out.[5] A negative antibody result, at the discretion of the responsible veterinarian, may require further confirmation that the animal is not in fact a PI.

At a herd level, a positive Ig result suggests that BVD virus has been circulating or the herd is vaccinated. Negative results suggest that a PI is unlikely however this naïve herd is in danger of severe consequences should an infected animal be introduced. Antibodies from wild infection or vaccination persist for several years therefore Ig ELISA testing is more valuable when used as a surveillance tool in seronegative herds.

Eradication and control

[edit]

The mainstay of eradication is the identification and removal of persistently infected animals. Re-infection is then prevented by vaccination and high levels of biosecurity, supported by continuing surveillance. PIs act as viral reservoirs and are the principal source of viral infection but transiently infected animals and contaminated fomites also play a significant role in transmission.[1]

Leading the way in BVD eradication, almost 20 years ago, were the Scandinavian countries. Despite different conditions at the start of the projects in terms of legal support, and regardless of initial prevalence of herds with PI animals, it took all countries approximately 10 years to reach their final stages.[26][27]

Once proven that BVD eradication could be achieved in a cost efficient way, a number of regional programmes followed in Europe, some of which have developed into national schemes.[28]

Vaccination is an essential part of both control and eradication. While BVD virus is still circulating within the national herd, breeding cattle are at risk of producing PI neonates and the economic consequences of BVD are still relevant. Once eradication has been achieved, unvaccinated animals will represent a naïve and susceptible herd. Infection from imported animals or contaminated fomites brought into the farm, or via transiently infected in-contacts will have devastating consequences.

Vaccination

[edit]

Modern vaccination programmes aim not only to provide a high level of protection from clinical disease for the dam, but, crucially, to protect against viraemia and prevent the production of PIs.[29] While the immune mechanisms involved are the same, the level of immune protection required for foetal protection is much higher than for prevention of clinical disease.[30]

While challenge studies indicate that killed, as well as live, vaccines prevent foetal infection under experimental conditions, the efficacy of vaccines under field conditions has been questioned.[31] The birth of PI calves into vaccinated herds suggests that killed vaccines do not stand up to the challenge presented by the viral load excreted by a PI in the field.[32]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Bovine viral diarrhea

View on Grokipedia
from Grokipedia
Bovine viral diarrhea (BVD), also known as bovine viral diarrhoea, is a contagious viral disease primarily affecting cattle of all ages, caused by the bovine viral diarrhea virus (BVDV), a single-stranded positive-sense RNA virus in the genus Pestivirus of the family Flaviviridae. The virus exists in two biotypes—noncytopathic and cytopathic—with the former typically responsible for persistent infections and the latter associated with severe acute disease, including the fatal mucosal disease complex. BVD leads to a spectrum of clinical manifestations, ranging from subclinical infections to acute symptoms such as fever (often 105–107°F), bloody diarrhea, oral ulcers, pneumonia, decreased milk production, and immunosuppression, which predisposes animals to secondary infections. In pregnant cattle, infection can cause reproductive failures including abortions, stillbirths, and the birth of persistently infected (PI) calves with congenital defects, where exposure before 125 days of gestation results in lifelong viral shedding without an effective immune response. Transmission of BVDV occurs mainly through direct or indirect contact with infected animals, particularly PI individuals that excrete high levels of in , , nasal discharges, , , and reproductive fluids, serving as the primary for sustained outbreaks. The can also spread via contaminated fomites such as water troughs, transport vehicles, or needles, as well as through or embryos in and programs, with an of 3–5 days. Interspecies transmission is possible to other ruminants like sheep, , and under close contact conditions, though remain the main host. While BVDV does not pose a direct zoonotic risk to humans, its endemic presence worldwide— with seroprevalence often exceeding 90% in vaccinated populations—makes it a major concern. Economically, imposes substantial losses on the global industry, estimated through reduced , increased of PI animals, treatment costs for secondary diseases, and mortality rates that can reach up to 50% in acute outbreaks, with PI prevalence typically ranging from 1%–2% in beef herds and up to 4% in operations. In some countries, is regarded as the single most important viral infection of due to its immunosuppressive effects and role in exacerbating other pathogens like or bovis. Control strategies emphasize eradication programs, including routine screening via ear-notch tests or PCR to identify and remove PI animals, alongside with modified-live or inactivated vaccines to boost , though no universal vaccine exists and remains essential. Successful national programs, such as those in , have demonstrated that early detection and can eliminate from herds within years.

Virology

Classification and taxonomy

Bovine viral diarrhea virus (BVDV) is classified within the family Flaviviridae and the genus Pestivirus. The genus Pestivirus encompasses enveloped, positive-sense single-stranded RNA viruses that primarily infect ungulates, with BVDV specifically associated with cattle and other ruminants. According to the International Committee on Taxonomy of Viruses (ICTV), the viruses causing BVD are classified into distinct species: Pestivirus bovis (BVDV-1; previously Pestivirus A), Pestivirus tauri (BVDV-2; previously Pestivirus B), and Pestivirus brazilense (HoBi-like pestivirus, also known as BVDV-3; previously Pestivirus H). Within these species, BVDV exhibits significant , characterized by multiple subtypes. Pestivirus bovis includes at least 23 subtypes (e.g., 1a through 1w), while Pestivirus tauri has at least four (2a through 2d); these subtypes are defined primarily by phylogenetic analysis of genes such as the (5'UTR) and envelope protein E2. As of 2025, the number of recognized subtypes continues to grow due to ongoing and sequencing efforts. Additionally, BVDV strains are categorized into two biotypes based on their cytopathic effects in : non-cytopathic (NCP), which do not induce and are responsible for persistent infections, and cytopathic (CP), which cause visible and are often associated with mucosal outbreaks. The CP biotype typically arises from mutations or recombination events in NCP strains. Pestivirus brazilense, identified more recently as a distinct , represents an emerging with HoBi-like characteristics, first detected in Italian cattle in 2007 and subsequently reported in regions including , , and . This shows genetic divergence from Pestivirus bovis and Pestivirus tauri, with identities around 75-80% in key genomic regions, highlighting the ongoing evolution within the . Phylogenetically, BVDV species form a monophyletic within Pestivirus, closely related to other members such as classical swine fever virus (Pestivirus C), with shared and antigenic due to conserved epitopes in structural proteins. Evolutionary analyses indicate that Pestivirus bovis and Pestivirus tauri diverged from a common ancestor around 500-1000 years ago, with Pestivirus brazilense as a more distant , reflecting host adaptation in ruminants while maintaining relatedness to suid-infecting pestiviruses like CSFV.

Genome and virion structure

Bovine viral (BVDV) is an enveloped with a spherical to semi-spherical morphology and a of approximately 40-60 nm. The virion consists of a envelope derived from the host , which embeds the viral glycoproteins, and an internal electron-dense core containing the genome packaged by the protein. Cryo-electron reveals a smooth surface without prominent , though surface projections are formed by the embedded glycoproteins Erns, E1, and E2, which exist primarily as E1-E2 heterodimers essential for entry. The genome of BVDV is a single-stranded, positive-sense RNA molecule approximately 12.3 kb in length. It features a single long open reading frame (ORF) encoding a polyprotein, flanked by a 5' untranslated region (UTR) of about 385 nucleotides and a 3' UTR of around 200-250 nucleotides. The 5' UTR contains an internal ribosome entry site (IRES) that facilitates cap-independent translation, while the 3' UTR includes stem-loop structures that contribute to RNA stability and replication initiation. The polyprotein is processed into four structural proteins and several non-structural proteins. Structural proteins include the protein C, which binds the genomic , and the envelope glycoproteins Erns (also known as E0), E1, and E2. Erns is a heavily glycosylated involved in envelope formation, E1 mediates fusion, and E2 serves as the primary attachment protein, featuring key domains such as receptor-binding sites that interact with host cell surface molecules. Non-structural proteins comprise Npro, an N-terminal autoprotease that modulates host responses; NS2 and NS3, which include and activities; NS4A and NS4B, aiding in rearrangements; and NS5A and NS5B, components of the replication complex with NS5B acting as the .

Replication and molecular biology

Bovine viral diarrhea virus (BVDV) initiates infection through , primarily binding to the bovine CD46 receptor via its E2 envelope , which facilitates attachment and subsequent internalization. Additional host factors, such as the receptor, may contribute to entry efficiency in certain cell types. The process involves clathrin-coated pits and is -dependent, with low in endosomes triggering membrane fusion and release of the viral genomic into the . Replication of BVDV occurs exclusively in the , independent of nuclear machinery, utilizing the virus-encoded NS5B to initiate . The positive-sense, single-stranded genome serves as a template for producing complementary negative-strand intermediates, which in turn direct the amplification of new genomic and subgenomic products for into viral proteins. This cytoplasmic replication complex, associated with host membranes like the , ensures efficient propagation without host DNA involvement. Assembly of infectious virions takes place at intracellular membranes, particularly the rough , where the core protein C encapsidates the genomic , and envelope glycoproteins Erns, E1, and E2 embed into lipid bilayers to form enveloped particles. These nascent virions bud into cytoplasmic vesicles derived from the ER-Golgi intermediate compartment and are transported to the plasma membrane for release via , maintaining the enveloped structure. Recent post-2020 has advanced understanding of the Npro non-structural protein's in immune evasion during replication. Npro acts as an autoprotease that ubiquitinates and targets regulatory factor 3 () for proteasomal degradation, thereby suppressing type I production and innate antiviral signaling. Studies have identified interactions with host proteins like CALCOCO2, which enhance Npro's inhibitory effects on IFN pathways, and genotype-specific molecular docking models revealing variations in evasion across BVDV strains.

Epidemiology

Transmission mechanisms

Bovine viral diarrhea (BVDV) primarily spreads through between animals in close proximity, as well as from to offspring. Horizontal routes involve direct contact with infected secretions or indirect exposure to contaminated materials, while occurs transplacentally during . Persistently infected (PI) animals serve as the principal reservoirs, continuously shedding high viral loads that facilitate sustained dissemination within and between herds. Direct transmission occurs via nasal, oral, ocular secretions, , , , , and or from acutely or persistently infected . These bodily fluids contain infectious particles that susceptible animals ingest or inhale during close contact, such as in shared feeding or housing spaces. PI animals, in particular, shed virus at titers of 10⁴ to 10⁶ CCID₅₀/mL lifelong, making them highly efficient transmitters even without overt clinical signs. Neighborhood contacts, including shared pastures, account for a significant portion of outbreaks, often comprising over 70% of new infections in susceptible populations. Indirect transmission happens through fomites such as contaminated equipment, needles, clothing, or environmental surfaces, which can harbor viable BVDV for extended periods under suitable conditions. This route enables spread between herds via shared veterinary procedures, transport vehicles, or human vectors. Trade movements of infected animals, including undetected PI individuals, contribute to inter-herd dissemination, particularly in regions with active markets. Vertical transmission is a critical mechanism for establishing PI carriers, occurring when a pregnant is exposed to non-cytopathic BVDV strains between days 40 and 125 of , before fetal develops. The crosses the , infecting the and inducing immunotolerance, resulting in that are born PI and shed continuously. This pathway perpetuates BVDV within herds, as PI calves often remain undetected until breeding or until they trigger secondary infections.

Global distribution and prevalence

Bovine viral diarrhea virus (BVDV) is ubiquitous in populations worldwide, with the virus established in nearly all countries where are raised. A comprehensive of 325 studies spanning 1961 to 2016 across 73 countries, involving over 6.5 million animals, revealed a global pooled of persistently infected (PI) at the individual level decreasing from 1.85% (95% CI: 0.65–3.59) in 1980 to 0.36% (95% CI: 0.23–0.51) in 2016, reflecting the impact of emerging control measures. Seroprevalence rates in endemic areas typically range from 20% to 90%, with a stable global average of approximately 46–49% at the animal level and 66–67% at the herd level during this period, though regional variations persist due to differences in and practices. Prevalence is generally higher in developing countries and regions with limited control programs, such as parts of , , and the , where PI rates often exceed 1.6% and seroprevalence can surpass 50–70% in unvaccinated herds. In contrast, developed regions with active eradication efforts show marked declines; for instance, PI prevalence remains low at ≤0.8% in , , and . Updates from 2020 to 2025 indicate continued reductions in vaccinated and monitored areas, with China's overall BVDV positive rate dropping to 6.05% by mid-2025 and Germany's reporting only 46 PI calves born in 2024. Eradication successes are notable in , where mandatory programs have accelerated progress toward BVDV-free status. Scotland's national scheme, legislated since and entering Phase 6 in July 2025, has reduced PI incidence to near elimination levels, with over 93% of breeding herds classified as negative by October 2025. Similarly, Ireland's program, supported by additional funding in 2025, aims for an 18-month period without confirmed positives to meet Animal Health Law requirements, building on substantial PI declines since . These efforts highlight how systematic testing and removal of PI animals—key reservoirs for transmission—have driven prevalence downward in targeted regions. While are the primary hosts, BVDV also affects sheep and , with meta-analyses estimating overall at 8.6% (95% CI: 5.2–12.7) via immunological detection and 7.3% (95% CI: 2.7–13.7) via virological methods across global flocks. species, including deer, wild ruminants, and , serve as potential reservoirs, with seroprevalence exceeding 60% in some populations like and in , facilitating spillover to domestic herds.

Economic and production impacts

Bovine viral diarrhea virus (BVDV) infections impose substantial economic burdens on the global cattle industry through direct production losses and indirect costs associated with disease management. A systematic review of 44 studies across 15 countries estimated direct monetary losses ranging from USD 0.50 to USD 687.80 per animal annually, with average losses of USD 199.50 per naïve dairy cow and USD 174.60 per beef cow, primarily driven by factors such as mortality, morbidity, premature culling, stillbirths, abortions, and reinfections. In the United States, persistent BVDV infections alone cost the beef industry an estimated USD 1.5 to 2.5 billion annually, highlighting the scale in major producing regions. These losses translate to reduced milk and meat yields, with infected herds showing weaning weights 5-10 kg lower per calf compared to uninfected ones. Reproductive inefficiencies further exacerbate financial impacts, including decreased conception rates by approximately 10-15% in exposed herds and elevated rates of early embryonic death and abortion. Calf mortality in acute outbreaks can reach 10-20%, contributing to substantial herd productivity declines; for instance, one documented outbreak resulted in a 44% loss of the calf crop due to reproductive failures and neonatal deaths. Fertility issues, such as prolonged calving intervals, compound these effects, leading to fewer marketable animals and lower overall herd output. Post-2020 studies emphasize , including trade and movement restrictions in BVDV eradication zones, which disrupt commerce and increase surveillance expenses. In European countries pursuing eradication, such as and the Netherlands, ongoing monitoring protocols post-eradication add millions in annual costs while preventing reintroduction, though they impose temporary limitations on animal transport in affected areas. Additionally, BVDV-induced heightens susceptibility to secondary infections like , amplifying losses by an estimated USD 800-900 million annually in the through treatment and reduced performance. These broader effects underscore the virus's role in escalating total economic impacts beyond direct production deficits.

Pathogenesis

Acute transient infection

Acute transient infection with bovine viral diarrhea virus (BVDV) occurs in previously unexposed, immunocompetent , typically resulting in a self-limiting viremic phase lasting 2-3 weeks. The ranges from 3 to 7 days post-exposure, during which the virus replicates in lymphoid tissues before disseminating systemically. Following incubation, acute infection is characterized by and transient , with virus detectable in blood and nasal secretions for up to 15 days and leukocyte counts often dropping sharply due to lymphoid depletion in tissues like the and Peyer's patches. This peaks around days 5-9 post-infection and contributes to a brief window of . The virus's Npro protein plays a key role in this by inhibiting type I production through degradation of interferon regulatory factor 3 (IRF-3), thereby dampening innate immune responses and predisposing animals to secondary bacterial or viral infections; recent studies have further elucidated roles of NS3 and NS5A proteins in suppression as part of broader immune evasion. Most acutely infected clear the virus through a robust humoral , with neutralizing antibodies appearing within 2-3 weeks and facilitating recovery by day 13-21 post-infection, as lymphoid tissues repopulate and resolves. Infections are often subclinical, with minimal clinical impact, but severity varies by strain; BVDV-2 isolates, particularly high-virulence subtypes, can induce more pronounced , , and severe outcomes compared to BVDV-1 strains.

Intrauterine infections

Intrauterine infection with bovine viral diarrhea virus (BVDV) occurs when the virus crosses the to infect the developing , with outcomes varying based on the gestational stage at exposure. Early infections, particularly between days 40 and 125, often result in persistently infected (PI) calves due to the 's immature failing to mount an effective response. In contrast, infections later in typically lead to abortions, stillbirths, or the birth of weak calves with transient infections that resolve postnatally. The development of PI calves is closely tied to exposure with non-cytopathic (ncp) BVDV strains during the critical window of , approximately days 60 to 125 of . At this stage, the fetal lacks competence to recognize and eliminate the , leading to central where the ncp BVDV is perceived as "self" rather than foreign. This tolerance arises from viral proteins such as Npro and Erns suppressing production and innate immune signaling, preventing activation of adaptive responses and allowing lifelong viral persistence without clearance. Consequently, PI calves are born viremic, shedding high levels of throughout their lives and serving as primary reservoirs for herd transmission. In addition to PI, intrauterine BVDV infection can induce teratogenic effects, particularly on the , when exposure occurs between gestation days 79 and 150. Common malformations include , characterized by reduced cerebellar size due to of the external granular layer, and , involving extensive cerebral tissue destruction replaced by fluid-filled cavities. These defects result from direct viral cytopathic effects on proliferating neural cells during vulnerable periods of , often co-occurring with other anomalies like or thymic . Fetuses surviving such infections may be born with neurological impairments affecting coordination and viability. Recent research since 2021 has revealed that even transient intrauterine BVDV infections can induce lasting epigenetic modifications in fetal tissues, influencing beyond the immediate viral presence. For instance, late-gestation infections (e.g., day 175) lead to differential in , with thousands of altered cytosines affecting pathways for fetal growth (e.g., WNT signaling) and immune function (e.g., Notch1 and IL-11 genes). These changes persist postnatally, correlating with reduced birth weights and potential long-term impacts on development and disease susceptibility, as seen in epigenomic analyses of PI and transiently infected calves. Such findings underscore the virus's broader influence on fetal programming, even in resolved infections.

Persistent infections

Persistent infections with bovine viral diarrhea (BVDV) arise exclusively from intrauterine exposure to the non-cytopathic (ncp) biotype during a critical window of fetal development, typically between 40 and 125 days of in . This timing precedes the maturation of the fetal , resulting in central immunotolerance where the developing T and B cells fail to recognize the as foreign, allowing lifelong viral persistence without eliciting an effective . Consequently, calves born from such infections become persistently infected (PI) animals that remain viremic and seronegative throughout their lives, serving as a primary for BVDV within herds. In PI cattle, the virus establishes continuous replication in various tissues, leading to high viral loads in , nasal and ocular secretions, , , , , and , with shedding occurring consistently at titers of 10^3 to 10^5 TCID50/mL. This persistent shedding facilitates efficient to susceptible herd mates and to offspring, perpetuating BVDV circulation without immune-mediated clearance due to the established tolerance. PI animals often appear clinically normal or exhibit subtle growth impairments, but their role in amplifying viral spread underscores their epidemiological significance. Superinfection of PI cattle with a cytopathic (cp) BVDV strain, which may arise as a of the resident ncp virus or from an external source, disrupts this tolerance and triggers the severe mucosal (MD) syndrome. The cp biotype induces widespread and inflammatory lesions in epithelial tissues, leading to erosive , , and high mortality rates approaching 100% in affected animals. This progression highlights the dual biotype dynamics in BVDV , where ncp sets the stage for cp-mediated exacerbation. The BVDV in PI animals demonstrates relative genetic stability, with low rates during persistent replication compared to acute infections, attributed to the absence of immune pressure that would otherwise drive rapid evolution. However, subtype variations persist, including differences between BVDV-1 and BVDV-2, and occasional recombination events can occur, contributing to quasispecies diversity within the host while maintaining overall virological fitness. This stability ensures efficient transmission but limits the emergence of novel variants in the PI context.

Clinical manifestations

Signs in acutely infected cattle

Acute infections with bovine viral diarrhea virus (BVDV) in cattle are often subclinical or mild, reflecting the virus's immunosuppressive effects that primarily manifest through transient immune dysregulation rather than direct cytopathic damage. Common clinical signs include pyrexia, typically ranging from 105°F to 107°F, which develops shortly after an incubation period of about 3 days; depression or lethargy; anorexia; and watery to mucoid diarrhea that contributes to dehydration in affected animals. Respiratory involvement is frequent, presenting as nasal and ocular discharges, mild coughing, or secondary pneumonia due to impaired neutrophil function and increased bacterial susceptibility. Oral lesions, such as erosions on the muzzle, gums, and hard palate, along with reduced milk yield in lactating cows, further characterize these infections, though the overall syndrome varies by host immune status and viral strain. In rare severe cases, particularly those caused by highly virulent BVDV-2 strains, acute infections progress to hemorrhagic diathesis marked by profound , epistaxis, bloody with mucosal casts, ecchymoses on mucous membranes, and gastrointestinal hemorrhages, often leading to acute fatalities within days of onset. These outbreaks, historically noted in during the , can affect calves and adults alike, with mortality rates exceeding 10-50% in naive herds, underscoring BVDV-2's greater thrombocytopenic potential compared to BVDV-1. Most acutely infected exhibit signs for 5-14 days before clears and recovery ensues, with surviving animals developing lifelong immunity to homologous strains. Young calves, especially those under 6 months with waning maternal antibodies, face heightened risk of severe or fatal disease due to immature lymphoid tissues and greater , whereas infections in adults over 2 years are typically self-limiting with minimal long-term sequelae.

Features of persistently infected animals

Persistently infected (PI) with bovine viral diarrhea (BVDV) harbor the lifelong due to fetal between days 40 and 125 of gestation, resulting in that allows continuous without clearance. These animals often present as unthrifty with poor growth and ill-thrift, characterized by reduced weight gain, chronic wasting, and suboptimal performance as "poor doers" throughout life. Clinical features in PI cattle include a reduced general condition in up to 93% of cases, alongside loss of appetite (94%) and ruminal hypoperistalsis (92%), leading to (63%) and recurrent (69%). Chronic affects approximately 20% of these animals, contributing to their overall ill-thrift and increased vulnerability to environmental stressors. Growth retardation is observed in about 30% of PI cattle, often linked to persistent that impairs nutrient utilization and recovery from infections. Many PI animals function as carriers, appearing clinically normal and indistinguishable from healthy mates without diagnostic testing, particularly in the absence of stress or co-infections. This subtlety poses significant identification challenges, as overt signs may only emerge under conditions like , , or disease outbreaks. However, PI exhibit heightened susceptibility to secondary pathogens, with gastrointestinal nematodes detected in 62% of examined cases, exacerbating their health decline. Mortality among PI calves is elevated, with approximately 50% dying within the first year of life from secondary diseases such as respiratory or enteric infections that progress more severely due to BVDV-induced . Surviving PI animals often require before reaching maturity owing to chronic poor performance and health risks.

Mucosal disease syndrome

Mucosal disease syndrome represents the acute, lethal endpoint of bovine viral diarrhea virus (BVDV) infection in cattle persistently infected (PI) with a non-cytopathic (ncp) strain, triggered by superinfection with a cytopathic (cp) strain or spontaneous to a cp biotype. This condition arises when the cp virus induces widespread cytopathic effects in already immunocompromised PI animals. The syndrome has a rapid onset following exposure to the cp strain, with clinical signs appearing within 1-2 weeks and progressing to death in most cases within another 1-2 weeks. Key manifestations include high fever, erosive with oral ulcers, severe gastrointestinal ulceration leading to bloody , anorexia, and profound . These symptoms reflect the virus's aggressive replication and tissue destruction, resulting in 100% mortality among affected animals. Pathologically, mucosal disease involves extensive epithelial across mucosal surfaces, particularly in the , accompanied by lymphocytolysis in lymphoid tissues such as Peyer's patches. Ulcerative and hemorrhagic lesions dominate, with loss of intestinal crypts and widespread mucosal sloughing contributing to the animal's rapid decline. The incidence of mucosal disease is rare in PI cattle, though it is invariably fatal in those cases. Recent molecular studies from the have highlighted the central role of the NS3 non-structural protein in mediating cytopathic effects, where its expression as a and promotes via activation and disrupts cellular in infected tissues.

Diagnosis

Antigen and virus detection methods

Antigen and detection methods are essential for identifying active bovine viral diarrhea (BVDV) infections, particularly in persistently infected (PI) , which serve as lifelong reservoirs of the . These techniques directly target viral proteins or infectious particles, enabling confirmation of current infection status without relying on immune responses. Common approaches include , isolation, and antigen-capture enzyme-linked immunosorbent assay (), each offering distinct advantages in sensitivity, specificity, and practicality for field or laboratory use. Immunohistochemistry (IHC) on ear notch skin biopsies is a widely adopted method for screening PI animals, as it detects BVDV antigens in epithelial tissues where the virus persists at high levels. The procedure involves collecting a small skin sample from the ear notch, fixing it, and with virus-specific antibodies to visualize infected cells under . This technique is particularly valuable for on-farm testing due to its non-invasive sampling and ability to preserve tissue morphology for retrospective analysis. IHC demonstrates high diagnostic sensitivity (>95%) and specificity for PI detection, making it reliable for identifying and infected individuals in eradication programs. Virus isolation in remains the gold standard for confirming infectious BVDV, especially non-cytopathic strains prevalent in PI cattle. The process entails inoculating serum, , or tissue samples onto susceptible bovine cell lines, such as Madin-Darby bovine kidney (MDBK) cells, and monitoring for over 1–3 passages, often confirmed by immunoperoxidase staining. While highly specific (~100%), its sensitivity is lower (<90%) compared to molecular methods, and it is labor-intensive, requiring specialized facilities and being susceptible to interference from maternal antibodies in young calves. This method is best suited for reference laboratories verifying ambiguous results from rapid tests. Antigen-capture ELISA provides a rapid, high-throughput alternative for detecting BVDV antigens, such as NS2-3 or Erns proteins, in serum, plasma, or bulk milk samples, facilitating herd-level screening. The assay uses monoclonal antibodies to capture viral antigens, followed by enzymatic detection for quantifiable results, often processable in under 2 hours. It exhibits diagnostic sensitivity of 67–100% and specificity of 98.8–100% relative to virus isolation, with minimal interference in older animals but reduced performance in calves under 3 months due to colostral antibodies. This method's field usability and cost-effectiveness make it ideal for monitoring dairy herds via bulk milk testing.
MethodSample TypeSensitivitySpecificityKey AdvantagesKey Limitations
Immunohistochemistry (IHC)Ear notch skin biopsy>95%>95%High accuracy for PI; tissue visualizationLabor-intensive; requires
Virus IsolationSerum, , tissues<90%~100%Confirms infectious virusTime-consuming; antibody interference
Antigen-Capture Serum, bulk 67–100%98.8–100%Rapid, high-throughputLess effective in young calves

Antibody detection assays

Antibody detection assays are serological methods used to identify immune responses to bovine viral diarrhea virus (BVDV) in , providing evidence of prior exposure, , or maternal immunity rather than active infection. These tests target specific antibodies such as (IgG) and (IgM), which indicate different stages of infection or immunity. They are particularly valuable for assessing status and monitoring efficacy, though they cannot detect the virus itself or distinguish between types in all cases. The serum neutralization (SN) test serves as the gold standard for detecting subtype-specific neutralizing against BVDV types 1 and 2. In this , serial dilutions of serum are incubated with a known quantity of BVDV, and the mixture is added to cell cultures; the highest dilution that prevents cytopathic effects determines the . SN assays offer high specificity for functional capable of blocking viral entry and replication, making them essential for confirming protective immunity following or natural . They are subtype-specific, allowing differentiation between BVDV-1 and BVDV-2 strains, though they are labor-intensive and require specialized labs. Enzyme-linked immunosorbent assays (ELISAs) provide a rapid, high-throughput alternative for detecting BVDV-specific IgG and IgM antibodies, ideal for herd screening and large-scale . IgM-capture ELISAs identify acute infections by detecting early IgM responses, typically present for 2-3 weeks post-infection, while IgG ELISAs signal chronic or resolved infections and are often used to evaluate overall herd exposure. Blocking ELISAs, such as those targeting the NS3 protein, further enhance specificity by competing antibodies with a recombinant , correlating well with SN titers for both BVDV subtypes. These assays are cost-effective and can analyze serum, plasma, or milk samples, facilitating routine monitoring in veterinary practice. Maternally derived antibodies transferred via can confound detection in newborn calves, resulting in false-positive serological results that reflect immunity rather than the calf's status. These passive antibodies, primarily IgG, persist for 3-6 months or longer depending on intake and calf age, masking the calf's own to or . To accurately assess calf-specific immunity, testing is recommended after maternal antibodies decline, typically beyond 6 months of age, or using paired samples to track changes. A key limitation of antibody detection assays is their inability to identify persistently infected (PI) animals, which fail to produce BVDV-specific antibodies due to central immunotolerance established during in utero infection. PI cattle remain seronegative even after prolonged exposure, necessitating complementary virus detection methods to rule out persistent infection in antibody-negative cases. This tolerance prevents humoral responses against the infecting strain, though superinfection with heterologous BVDV may occasionally induce detectable antibodies.

Molecular diagnostic techniques

Molecular diagnostic techniques for bovine viral diarrhea virus (BVDV) primarily involve nucleic acid-based methods that target the viral , enabling direct detection of the in clinical samples such as , tissues, , and aborted fetuses. These approaches, including (RT-PCR) and its variants, offer high specificity and sensitivity by amplifying specific regions of the BVDV , such as the (5' UTR) or the NS5B gene, which are conserved across genotypes. Unlike detection, molecular methods detect viral genetic material regardless of , making them particularly useful for identifying persistently infected (PI) animals and early-stage infections. Conventional RT-PCR converts BVDV RNA to followed by amplification, allowing detection of the virus in samples where viral loads may be low. This technique has been widely adopted for routine diagnostics due to its ability to confirm BVDV presence through visualization of amplicons, with primers targeting the 5' UTR providing broad coverage for genotypes 1 and 2. Studies have shown RT-PCR to be more sensitive than virus isolation, detecting BVDV in ear notch samples from PI calves with over 95% agreement compared to isolation methods. For , RT-PCR amplicons can be sequenced to differentiate BVDV-1 subtypes (e.g., 1a, 1b) and BVDV-2, aiding in epidemiological surveillance. Real-time reverse transcription quantitative PCR (RT-qPCR), often using probes, enhances detection by quantifying viral in real-time through signals, eliminating the need for post-amplification processing and reducing contamination risks. This method targets the same genomic regions as conventional RT-PCR but provides cycle threshold (Ct) values for semi-quantitative assessment of , with limits of detection as low as 10 viral copies per reaction, ideal for low-load infections in acute or transient cases. RT-qPCR assays have demonstrated superior performance over antigen in pooled blood samples, detecting BVDV in up to 1:100 dilutions for herd screening, and are recommended by veterinary guidelines for confirming PI status. To confirm PI status, animals testing positive should be retested after 3 weeks using the same method. Post-2020 advancements include multiplex RT-qPCR assays that simultaneously detect BVDV alongside other calf diarrhea pathogens like rotavirus or coronavirus, using multiple probes for rapid syndromic screening in veterinary labs. Emerging isothermal methods, such as reverse transcription loop-mediated isothermal amplification (RT-LAMP) and recombinase polymerase amplification (RT-RPA), enable rapid detection in under 60 minutes without thermal cycling, suitable for field use. Additionally, CRISPR-Cas systems offer ultrasensitive, specific detection. These multiplex formats maintain high sensitivity (detecting <50 copies/reaction) while enabling subtyping through melt curve analysis or probe-specific signals, facilitating outbreak investigations. Pooled sample testing via RT-qPCR has improved efficiency for large-scale surveillance, with protocols optimizing RNA extraction from up to 50 ear notches per pool without significant loss in detection rates. Additionally, next-generation sequencing (NGS) of RT-PCR products or full genomes has emerged for strain identification, revealing phylogenetic relationships and tracking variants like BVDV-1d in endemic regions.

Prevention and control

Vaccination approaches

remains a of bovine viral diarrhea virus (BVDV) prevention, with several types available to induce protective immunity against acute infections and fetal transmission. Modified-live virus (MLV) , which contain attenuated BVDV strains, are widely used due to their ability to stimulate robust cell-mediated and humoral responses, mimicking natural infection for long-lasting protection. However, MLV carry a of inducing persistent infections (PI) in fetuses if administered to pregnant , necessitating careful timing to avoid use during . In contrast, killed (inactivated) vaccines are safer for pregnant animals, as they cannot replicate or cause , but they generally provide inferior compared to MLV, often requiring adjuvants and multiple doses for efficacy. Killed vaccines reduce clinical signs and but show lower protection against fetal infection, with studies indicating higher infection rates in vaccinated dams relative to MLV. Subunit vaccines, particularly those based on the immunogenic E2 , offer a targeted alternative by eliciting neutralizing antibodies without risks, making them suitable for pregnant cows; recent formulations have demonstrated enhanced protection when combined with adjuvants. Efficacy of BVDV vaccines varies by type and challenge, with MLV vaccines achieving 72-90% reduction in morbidity and 80-100% in mortality among young cattle, alongside 22-100% against fetal infection depending on timing and strain match. Killed vaccines reduce mortality but are less effective against morbidity, while subunit E2 vaccines have shown up to 94% fetal in challenge trials. Recent studies highlight cross- against BVDV subtypes 1 and 2, with MLV and subunit vaccines reducing clinical disease and viral circulation by 70-90% in diverse challenge models, though antigenic variability can limit . Standard protocols emphasize pre-breeding to maximize fetal , with MLV administered at and 4-6 weeks prior to breeding in non-pregnant heifers and cows, followed by annual boosters in open animals. For killed vaccines, a two-dose primary series 3-4 weeks apart is recommended, with the final dose at least one month before breeding and semi-annual boosters thereafter to sustain immunity. In herds with unknown status, initial should include boosters 2-4 weeks apart, prioritizing MLV for non-pregnant stock while using killed or subunit options during .

Biosecurity and management strategies

Biosecurity measures are essential for preventing the introduction and limiting the spread of bovine viral diarrhea virus (BVDV) within herds, focusing on physical isolation, testing, and to disrupt transmission routes such as contact and contaminated fomites. These strategies emphasize proactive management at the farm level to protect susceptible animals, particularly pregnant cows and neonates, from exposure that could lead to persistently infected (PI) calves. Quarantine protocols for new animals typically involve isolating purchases for at least 30 days in a separate facility, at least 30 feet from the resident herd, with no shared airspace, water, or equipment to monitor for signs of infection and allow for testing. All incoming cattle should be tested for BVDV antigen or virus prior to integration, with negative results required before commingling; in the UK, testing must occur within 20 days of arrival, and only BVD-negative animals can move to other herds. This approach minimizes the risk of introducing PI carriers, which are the primary source of ongoing virus shedding. In calf rearing, separating neonates from adult cattle is critical to avoid exposure during the vulnerable period before maternal antibodies wane, with individual housing in hutches spaced at least 4 feet apart recommended until . management should prioritize feeding from tested, low-risk within the herd, avoiding pooling or sourcing from external farms to prevent transmission of BVDV via infected , and can further reduce risks if necessary. All newborn calves, especially those from year-round calving systems, should be tested for PI status shortly after birth to enable early isolation. Hygiene practices include routine disinfection of calving areas, feeding equipment, and vehicles between uses, using approved agents effective against enveloped viruses like , and implementing footbaths for personnel entering calf facilities. Avoiding shared needles and syringes is a key measure, with disposable equipment mandated for injections, dehorning, or other procedures to eliminate iatrogenic transmission. The prompt identification and removal of PI animals form the cornerstone of herd-level control, with confirmed PI cattle culled immediately after testing to halt virus circulation; in guidelines updated in 2024, this includes culling the dam of any PI calf and imposing movement restrictions starting in 2025. EU-wide analyses reinforce PI removal as a high-impact strategy, particularly in voluntary control programs in countries like and , where it has supported herd-level eradication efforts.

Eradication and surveillance programs

Eradication programs for bovine viral diarrhea (BVDV) have been implemented across various regions, primarily in , through a combination of voluntary and compulsory schemes aimed at systematic virus elimination. The Scandinavian countries—, , , and —pioneered large-scale efforts starting in the , employing a model that integrates initial herd screening for persistently infected (PI) animals, measures, and ongoing monitoring to achieve national eradication. These programs classify herds as BVDV-free based on serological and virological testing of youngstock, followed by mandatory of PI animals and restrictions on movements from infected herds. By the early , these nations had successfully eradicated BVDV, serving as a blueprint for subsequent initiatives. In the , the Health Certification Standards (CHeCS) framework supports voluntary BVDV control through accredited health schemes, such as the Accredited Free program, which certifies herds as BVDV-free after annual testing and PI removal. Scotland's industry-led eradication scheme, now in Phase 6 as of July 2025, mandates annual testing and reporting, with compulsory measures for non-compliant herds. introduced a compulsory program in 2016 under the Bovine Viral Diarrhoea Eradication Scheme Order, requiring tissue tag testing of all calves and PI , with new effective February 2025 imposing herd restrictions on positive cases. is set to implement mandatory controls in 2027, including compulsory testing of breeding and PI removal, aligning with broader UK efforts. Germany's nationwide compulsory program, enforced since 2011, similarly requires ear-notch testing of calves and rapid PI elimination. Surveillance under these programs relies on mandatory reporting of test results to national authorities and systematic screening to detect PI animals. Tissue tagging, where a sample is collected via the calf's at birth, enables early identification and of PI calves, as implemented compulsorily since 2013 and extended through 2025. In the , annual herd-level testing and reporting ensure ongoing monitoring, with status updates required after any positive detection. These protocols facilitate PI within specified timelines, typically 21 days post-identification, to prevent transmission. By 2025, significant progress toward eradication has been achieved in parts of , with maintaining BVDV-free status since the early 2000s and reporting only 46 PI calves born in 2024, a drastic reduction from pre-program levels. The Dutch program increased BVDV-free herds from 59% in 2018 to 89% by 2023, while Ireland's initiative has reduced PI prevalence to under 0.1% of tested calves. In contrast, eradication efforts face substantial challenges in and , where BVDV prevalence remains high due to limited organized programs and . A global indicates seroprevalences exceeding 50% in many Asian and African populations, driven by uncontrolled animal movements and diagnostic gaps in low- and middle-income countries. Economic barriers, including the high cost of testing and PI removal without subsidies, hinder progress in these regions. Central to these programs are database systems for tracking herd status and animal movements, such as Ireland's national database, which logs all test results to enforce compliance and monitor progress. Economic incentives, including government subsidies for PI and testing costs, encourage farmer participation; for instance, Ireland allocated additional funding in 2025 to offset surveillance expenses and support eradication. Such measures have proven effective in sustaining voluntary engagement while transitioning to compulsory frameworks.

References

  1. https://www.woah.org/en/disease/bovine-viral-diarrhoea/
  2. https://www.merckvetmanual.com/infectious-diseases/bovine-viral-diarrhea/bovine-viral-diarrhea-and-mucosal-disease-complex
  3. https://www.vet.cornell.edu/animal-health-diagnostic-center/programs/nyschap/modules-documents/bovine-viral-diarrhea-background-management-and-control
  4. https://ictv.global/report/chapter/flaviviridaeport/flaviviridaeport/flaviviridae/pestivirus
  5. https://ictv.global/report/chapter/flaviviridae/flaviviridae/speciesnames
  6. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1370050/full
  7. https://journals.asm.org/doi/10.1128/mra.01150-24
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC5656787/
  9. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1222292/full
  10. https://www.sciencedirect.com/science/article/pii/S0042682208008040
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC8160231/
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC12512747/
  13. https://pmc.ncbi.nlm.nih.gov/articles/PMC1440463/
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC6340029/
  15. https://pmc.ncbi.nlm.nih.gov/articles/PMC2258937/
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC384763/
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC12302146/
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC136515/
  19. https://pmc.ncbi.nlm.nih.gov/articles/PMC10115221/
  20. https://pmc.ncbi.nlm.nih.gov/articles/PMC10730213/
  21. https://onlinelibrary.wiley.com/doi/10.1111/jvim.15816
  22. https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-019-0647-x
  23. https://www.nature.com/articles/s41598-018-32831-2
  24. https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-025-04491-8
  25. https://www.sciencedirect.com/science/article/pii/S0378113525003323
  26. https://www.gov.scot/publications/scottish-bvd-eradication-scheme/
  27. https://www.gov.ie/en/department-of-agriculture-food-and-the-marine/press-releases/minister-heydon-announces-additional-financial-support-for-farmers-towards-bvd-eradication/
  28. https://pmc.ncbi.nlm.nih.gov/articles/PMC8639873/
  29. https://bmcvetres.biomedcentral.com/articles/10.1186/1746-6148-8-204
  30. https://naes.unr.edu/research/project.aspx?GrantID=710
  31. https://doi.org/10.1016/j.tvjl.2017.01.005
  32. https://doi.org/10.1016/j.theriogenology.2006.04.016
  33. https://portal.nifa.usda.gov/web/crisprojectpages/1019423-bvdv-compromises-fetal-immune-organ-development-leading-to-post-natal-predisposition-to-secondary-infections.html
  34. https://www.zoetis.com.au/all-products/portal-site/beef-dairy-sheep/pdf/bvdv-guidelines-edition-3_hr-final.pdf
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC5674437/
  36. https://journals.sagepub.com/doi/10.1177/0300985813520250
  37. https://journals.asm.org/doi/10.1128/jvi.80.2.900-911.2006
  38. https://pmc.ncbi.nlm.nih.gov/articles/PMC12474344/
  39. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2018.00024/full
  40. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2021.665128/full
  41. https://www.mdpi.com/2076-0817/7/2/54
  42. https://journals.physiology.org/doi/full/10.1152/physiolgenomics.90276.2008
  43. https://pmc.ncbi.nlm.nih.gov/articles/PMC4581091/
  44. https://www.dvm360.com/view/reproductive-consequences-infection-with-bovine-viral-diarrhea-virus-proceedings
  45. https://www.mdpi.com/1999-4915/16/5/721
  46. https://pmc.ncbi.nlm.nih.gov/articles/PMC12049026/
  47. https://avmajournals.avma.org/view/journals/javma/219/5/javma.2001.219.629.pdf
  48. https://www.tahc.texas.gov/news/brochures/TAHCFactsheet_BVD.pdf
  49. https://extension.msstate.edu/publications/what-you-should-know-about-bovine-viral-diarrhea-cattle
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC7517858/
  51. https://www.sciencedirect.com/topics/immunology-and-microbiology/bovine-viral-diarrhea-virus-2
  52. https://avmajournals.avma.org/view/journals/ajvr/66/10/ajvr.2005.66.1738.pdf
  53. https://www.ncbi.nlm.nih.gov/books/NBK2491/
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC7117366/
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC9131992/
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC2850149/
  57. https://www.cabidigitallibrary.org/doi/full/10.1079/cabicompendium.74228
  58. https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1282526/full
  59. https://www.woah.org/fileadmin/Home/fr/Health_standards/tahm/3.04.07_BVD.pdf
  60. https://journals.sagepub.com/doi/pdf/10.1177/104063870701900105
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC11707765/
  62. https://pmc.ncbi.nlm.nih.gov/articles/PMC11026595/
  63. https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-021-02747-7
  64. https://www.mdpi.com/1999-4915/17/10/1295
  65. https://journals.sagepub.com/doi/full/10.1177/1040638717753962
  66. https://www.sciencedirect.com/science/article/pii/S0378113524000075
  67. https://www.cabidigitallibrary.org/doi/pdf/10.5555/20193311195
  68. https://pmc.ncbi.nlm.nih.gov/articles/PMC11810931/
  69. https://www.elsevier.es/en-revista-revista-argentina-microbiologia-372-articulo-improvement-bovine-pestiviral-diagnosis-by-S0325754122001043
  70. https://journals.asm.org/doi/10.1128/jcm.00167-14
  71. https://www.mdpi.com/1422-0067/25/16/8734
  72. https://www.dovepress.com/efficacy-of-vaccination-with-the-divence-vaccine-against-bovine-viral--peer-reviewed-fulltext-article-VMRR
  73. https://pubmed.ncbi.nlm.nih.gov/25447148/
  74. https://www.vet.cornell.edu/animal-health-diagnostic-center/programs/nyschap/modules-documents/bovine-viral-diarrhea-control-procedures
  75. https://pmc.ncbi.nlm.nih.gov/articles/PMC7134781/
  76. https://www.daera-ni.gov.uk/sites/default/files/2025-01/BVD%20Code%20of%20Good%20Practice_1.PDF
  77. https://stocfree.eu/sites/default/files/documents/publications/published%20risk%20factors%20meta%20analysis.pdf
  78. https://www.mdpi.com/2076-0817/10/10/1292
  79. https://www.sciencedirect.com/science/article/abs/pii/S0167587705002333
  80. https://www.avensonline.org/wp-content/uploads/JVSM-2325-4645-07-0041.pdf
  81. https://ahdb.org.uk/bvd
  82. https://www.gov.scot/publications/bovine-viral-diarrhoea-bvd/
  83. https://www.daera-ni.gov.uk/articles/bovine-viral-diarrhoea-bvd
  84. https://llmfarmvets.co.uk/implementation-of-mandatory-bvd-control-in-england-a-new-era-for-livestock-health-2027/
  85. https://pmc.ncbi.nlm.nih.gov/articles/PMC8204052/
  86. https://www.sciencedirect.com/science/article/pii/S0022030224013912
  87. https://animalhealthireland.ie/assets/uploads/2025/04/BVD_KeyMessages_2025_Final.pdf
  88. https://animalhealthireland.ie/programmes/bvd/bvd-key-messages/
  89. https://pmc.ncbi.nlm.nih.gov/articles/PMC6582812/
  90. https://pmc.ncbi.nlm.nih.gov/articles/PMC9404877/
  91. https://pmc.ncbi.nlm.nih.gov/articles/PMC5738591/
Add your contribution
Related Hubs
Contribute something
User Avatar
No comments yet.