Systems analysis of West Nile virus infection

Abstract

Emerging and re-emerging mosquito-borne viruses continue to pose a significant threat to human health throughout the world. Over the past decade, West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused annual epidemics of virus-induced encephalitis, hemorrhagic fever\shock syndromes, and arthritis, respectively. Currently, no specific antiviral therapies or vaccines exist for use in humans to combat or prevent these viral infections. Thus, there is a pressing need to define the virus-host interactions that govern immunity and infection outcome. Recent technological breakthroughs in 'omics' resources and high-throughput based assays are beginning to accelerate antiviral drug discovery and improve on current strategies for vaccine design. In this review, we highlight studies with WNV and discuss how traditional and systems biological approaches are being used to rapidly identify novel host targets for therapeutic intervention and develop a deeper conceptual understanding of the host response to virus infection.

Figure 1

Systems analysis to study the host response to emerging mosquito-borne viruses. (a) Schematic representing the host immune response to virus infection. (b) Traditional scientific methodologies to study the immune response to virus infection have predominantly involved knockout mouse, cell culture, ex vivo infection analysis and the use of a reverse genetics systems to manipulate viruses. Integrating this approach with systems biology and high-throughput based assays can provide a platform to accelerate identification of host targets of therapeutic intervention and improve on current strategies for vaccine design.