title: Dengue virus therapeutic intervention strategies based on viral, vector and host factors involved in disease pathogenesis.
abstract: Dengue virus (DV) is the most widespread arbovirus, being endemic in over 100 countries, and is estimated to cause 50 million infections annually. Viral factors, such as the genetic composition of the virus strain can play a role in determining the virus virulence and subsequent clinical disease severity. Virus vector competence plays an integral role in virus transmission and is a critical factor in determining the severity and impact of DV outbreaks. Host genetic variations in immune-related genes, including the human leukocyte antigen, have also been shown to correlate with clinical disease and thus may play a role in regulating disease severity. The host's immune system, however, appears to be the primary factor in DV pathogenesis with the delicate interplay of innate and acquired immunity playing a crucial role. Although current research of DV pathogenesis has been limited by the lack of an appropriate animal model, the development of DV therapeutics has been a primary focus of research groups around the world. In the past decade advances in both the development of vaccines and anti-virals have increased in dramatically. This review summarises the current understanding of viral, vector and host factors which contribute to dengue virus pathogenesis and how this knowledge is critically important in the development of pharmaceutical interventions.
authors.affiliation: Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Herrero
authors.forename: Andrew
authors.initials: A
authors.lastname: Zakhary
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Gahan
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Nelson
authors.forename: Belinda L
authors.initials: BL
authors.lastname: Herring
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hapel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
authors.forename: Maheshi
authors.initials: M
authors.lastname: Obeysekera
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Sheng
authors.forename: Adam
authors.initials: A
authors.lastname: Taylor
authors.forename: Stefan
authors.initials: S
authors.lastname: Wolf
authors.forename: Jayaram
authors.initials: J
authors.lastname: Bettadapura
authors.forename: Shobha
authors.initials: S
authors.lastname: Broor
authors.forename: Lalit
authors.initials: L
authors.lastname: Dar
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003715:Dengue / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D020022:Genetic Predisposition to Disease; D058605:Host-Derived Cellular Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007303:Insect Vectors; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D058605:Host-Derived Cellular Factors; D014764:Viral Proteins; D014765:Viral Vaccines