Dengue virus

Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Orthoflavivirus. Four serotypes of the virus have been found, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, the mainstream scientific community's understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

Dengue virus has increased dramatically within the last 20 years, becoming one of the worst mosquito-borne human pathogens that tropical countries have to deal with. Estimates published in 2013 indicate that as many as 390 million infections occur each year, and many dengue infections are increasingly understood to be asymptomatic or subclinical.

Based on the analysis of the envelope protein, at least three genotypes (1 to 3) are known. In 2013, a fourth serotype was reported. A single report of a fifth serotype DEN-5 in 2015 has not been replicated or further reported on. The rate of nucleotide substitution for this virus has been estimated to be 6.5×10⁻⁴ per nucleotide per year, a rate similar to other RNA viruses. The American African genotype has been estimated to have evolved between 1907 and 1949. This period includes World War I and World War II, which were associated with considerable movement of populations and environmental disturbance, factors known to promote the evolution of new vector-borne viral species.^{[citation needed]}

A Bayesian analysis of all four serotypes estimated that their most recent common ancestor existed about 340 AD (95% confidence interval: 280 BC–850 AD).

Until a few hundred years ago, Dengue virus was transmitted in sylvatic cycles in Africa, Southeast Asia and South Asia between mosquitoes of the genus Aedes and nonhuman primates, with rare emergences into human populations. The global spread of Dengue virus, however, has followed its emergence from sylvatic cycles and the primary lifecycle now exclusively involves transmission between humans and Aedes mosquitoes. Vertical transmission from mosquito to mosquito has also been observed in some vector species. Dogs have been found to be infected by the virus, but more research is needed to determine if dogs or other animals can serve as reservoirs or are just incidental hosts.

After the mosquito takes up infected blood from a human, the virus infects the mosquito's gut and other tissues. The infected mosquito then seeks blood, biting a different human. At this moment, the human's skin cells get (keratinocytes) infected first. Subsequently, dendritic cells (DC) take up the virus and get infected too. The DC's mobility disperses virus in the body where some other cell types can get infected, as well (macrophages, hepatocytes and Bone Marrow cells).

Dengue virus lifecycle in cells, both in arthropod and mammalian cells, is typical for single-stranded (+)-RNA viruses. After binding to specific receptors on the cell the virion gets endocytosed. Endosomes usually get acidified and become lysosomes which digest their content. But the acidic condition triggers a conformational change in the envelope of the virion, making its membrane fuse with the endosome membrane, releasing the viral capsid with the viral RNA genome into the cell's cytosol.

Viral RNA is capped and, so, cannot be distinguished from human mRNA. It gets translated by the cell's ribosomes into a polyprotein with 3,391 amino acids. This polyprotein cleaves itself to produce, after several steps, three structural (C, E, prM) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). All non-structural proteins are necessary to together create the viral replication complex (RC) which makes copies of capped viral RNA to produce more polyprotein and new virions. New virions move to exocytic vesicles via the secretory pathway and, there, get their mature form before they are released from the cell. One infected cell may release up to between 1,000 and 10,000 new virions.