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 Flavivirus. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic, as rather than distinct antigenic groups there appears to be a continuum. 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 (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic, as rather than distinct antigenic groups there appears to be a continuum. 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 with which tropical countries have to deal. Current estimates 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 four genotypes (1 to 4) are known. In 2013, a fifth serotype was reported. 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. 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 and 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. Recent findings suggest that, as the virus infects human cells, host homeostatic processes such as autophagy and ER stress response, not to mention apoptosis, are triggered depending on the infected cell type. The activation of autophagy and ER stress during infection enhances virus reproduction. Attempts to provide detailed summaries of the life cycle of dengue at the cellular level are published in review articles from different research groups. The DENV genome is about 11000 bases of positive-sense, single stranded RNA (ssRNA) that codes for three structural proteins (capsid protein C, membrane protein M, envelope protein E) and seven nonstructural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5). It also includes short non-coding regions on both the 5' and 3' ends. The DENV E (envelope) protein, found as a dimer on the surface of the mature viral particle, is important in the initial attachment of this particle to the host cell. Each E protein monomer comprises three ectodomains, ED1 to ED3, and a transmembrane segment. ED2 includes the dimerization interface, two glycosylation sites, and the peptide of fusion with the cellular membrane. ED3 is a continuous polypeptide segment; its fold is compact and immunoglobulin-like. Dengue virus is transmitted by a mosquito genus known as Aedes. Several molecules that interact with the viral E protein (ICAM3-grabbing nonintegrin, CD209, Rab 5, GRP 78, and the mannose receptor) have been shown to be important factors mediating attachment and viral entry. The membrane form of ribosomal protein SA may also be involved in the attachment. Recombinant domains of the E protein are used as well-defined antigens in the serological detection of antibodies directed against Dengue virus and as immunogens in vaccine candidates. The DENV prM (membrane) protein, which is important in the formation and maturation of the viral particle, consists of seven antiparallel β-strands stabilized by three disulfide bonds.