Dengue Virus 2 Envelope Products

Dengue virus is a single -stranded, positive-sense RNA virus belonging to the Flavivirdae family and is the causative agent of Dengue fever (1-3). Other viruses in the same family include Japanese encephalitis virus, West Nile virus, and yellow fever (2,3). The Dengue virus is primarily transmitted through Aedes mosquito bites, with 100-400 million people infected annually and approximately 20,000 deaths worldwide per year (1,3). There are four known Dengue virus serotypes (DENV 1-4) that share 65% amino acid sequence similarity (1-2). The serotypes can be further classified into genotypes according to geographical distribution (2,3). The structure of the Dengue virus is ~50 nanometers (nm) in diameter, spherical in shape, and consists of an enveloped single-stranded RNA, an icosahedral nucleocapsid core, and a lipid bilayer (1-3). The Dengue virus genome is 11-kilobases (kb) long and has a 5' untranslated region (UTR), an open reading frame (ORF), and a 3' UTR (1,3). The ORF encodes a polyprotein for the translation of the three structural proteins and seven non-structural proteins (1-3). The structural proteins are the capsid (100 amino acids (aa), 12 kilodalton (kDa)), the pre-membrane (166 aa) or membrane (75 aa, 8.2-8.5 kDa), and envelope (495 aa, 53 kDa) (1-3). The nonstructural proteins are NS1 (350 aa, 45 kDa), NS2A (218 aa, 22 kDa), NS2B (130 aa, 14 kDa), NS3 (618 aa, 70 kDa), NS4A (150 aa, 16 kDa), NS4B (245-249 aa, 27 kDa), NS5 (900 aa, 104 kDa) (1-3).

Dengue virus entry into host cells occurs via receptor-mediated endocytosis by receptor molecules including the mannose receptor, heparan sulfate, glycosaminoglycans, and DC-SIGN (1,3). Following attachment, the virus is endocytosed in clathrin-coated vesicles (1,3). Following internalization, clathrin disassembles and endosomal processing occurs, allowing viral fusion, disassembly, and release of viral RNA (1,3). This release results in viral translation and replication, virus assembly and maturation, and eventual exocytosis of the mature virus (1,3). Infection can result in a wide range of clinical symptoms including mild disease such as Dengue fever which is characterized by fever, headache, joint pain, rash, and retro-orbital pain, or severe, life-threatening conditions like Dengue hemorrhagic fever or Dengue shock syndrome which involves vascular permeability and leakage (1-3). Host immune response against infection includes innate immune response via interferon secretion and pro-inflammatory cytokine production, as well as adaptive immune response involving cellular and humoral components like T cell activation and B-cell mediated antibody production (1-3). As far as treatment for Dengue virus infection, there no commercial antiviral agents, though some anti-pyretics and certain phenolic compounds do show promise in treating infection (1-3). However, Resveratol, an antiviral for other Flavivirus, has been shown to directly attack the Dengue virus genome (1). While more work needs to be done, there are some live-attenuated tetravalent Dengue virus vaccine candidates in clinal trials including DENVax and TV003/TV005 (1-3).

References

1. Nanaware N, Banerjee A, Mullick Bagchi S, Bagchi P, Mukherjee A. Dengue Virus Infection: A Tale of Viral Exploitations and Host Responses. Viruses. 2021;13(10):1967. Published 2021 Sep 30. https://doi.org/10.3390/v13101967

2. Harapan H, Michie A, Sasmono RT, Imrie A. Dengue: A Minireview. Viruses. 2020;12(8):829. Published 2020 Jul 30. https://doi.org/10.3390/v12080829

3. Roy SK, Bhattacharjee S. Dengue virus: epidemiology, biology, and disease aetiology. Can J Microbiol. 2021;67(10):687-702. https://doi.org/10.1139/cjm-2020-0572