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Background
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West Nile Virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, yellow fever virus, and Dengue virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. It has rapidly spread across the United States with cases being observed in every continental state. Virus particles consist of a dense core made up of the core/capsid protein encapsulating the RNA genome surrounded by a membrane envelope embedded with envelope and matrix proteins. However, when the viruses are inside of infected cells, the matrix protein exists in its "pre-M" form as a heterodimer with the envelope proteins. Cleavage of the "pre-M protein to its mature form occurs during release of the virus, this cleavage leads to the dissociation of the heterodimers. The viral core protein is thought to contribute to the WNV-associated inflammation via apoptosis induced though the caspase-9 pathway as delivery of core gene delivery into the striatum of mouse brain and skeletal muscle resulted in cell death and inflammation. The highly glycosylated envelope protein was shown to play a major role for WNV entry into target cells as WNV entry was inhibited by using a recombinant domain III from the envelope glycoprotein. The WNV receptor has recently been identified as alpha v beta 3 integrin.
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