Role of host cell factors in flavivirus infection: Implications for pathogenesis and development of antiviral drugs.
The genus Flavivirus contains approximately 70 arthropod-borne enveloped RNA viruses many of which cause severe human and in some cases, animal disease. They include dengue virus, yellow fever virus, West Nile virus, Japanese encephalitis virus, and tick-borne encephalitis virus. Hundreds of thousands of deaths due to flavivirus infections occur each year, many of which are unpreventable due to lack of availability of appropriate vaccines and/or antiviral drugs. Flaviviruses exploit the cytoplasmic cellular machinery to facilitate propagation of infectious progeny virions. They engage in dynamic and antagonistic interactions with host cell membranes and biochemical processes. Following infection, the cells initiate various antiviral strategies to counteract viral invasion. In its defense, the virus has alternative strategies to suppress these host responses to infection. The fine balance between these interactions determines the outcome of the viral infection and disease progression. Published studies have revealed specific effects of flaviviruses on cellular processes, but the underlying mechanisms that determine the specific cytopathogenetic changes induced by different flaviviruses have not, as yet, been elucidated. Independently of the suppression of the type I IFN response which has been described in detail elsewhere, this review focuses on recent discoveries relating to alterations of host metabolism following viral infection. Such studies may contribute to new approaches to antiviral drug development. The role of host cellular factors will be examined in the context of protection and/or pathogenesis resulting from flavivirus infection, with particular emphasis on West Nile virus and dengue virus.
Pastorino
Boris
B
Unité des Virus Emergents, UMR190 "Emergence des pathologies virales" Université de la Méditerranée, Institut de Recherche pour le Développement, Faculté de Médecine, Marseille, France.
Nougairède
Antoine
A
Wurtz
Nathalie
N
Gould
Ernest
E
de Lamballerie
Xavier
X
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005416:Flavivirus / Q000472:pathogenicity*; D018177:Flavivirus Infections / Q000188:drug therapy* / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans
D000998:Antiviral Agents