NS1 = Colocalizes with NS1 and Can Substitute for NS1 in West Nile Virus Replication

NS1 = is a C-terminally extended formof theNS1 protein produced only by encephalitic flaviviruses from the Japanese encephalitis vi-rus serogroup. Here we show thatWest Nile virus (WNV)NS1 = andNS1 localize to the same cellular compartments when ex-pressed from plasmid DNAs and also colocalize to viral RNA replication sites in infected cells. Using complementation analysis with NS1-deleted WNV cDNA, we demonstrated that NS1 = is able to substitute for the crucial function of NS1 in virus replication. West Nile virus (WNV) is a mosquito-borne flavivirus withinthe Japanese encephalitis virus (JEV) serogroup. This sero-group also includes other encephalitic flaviviruses, such as JEV, Murray Valley encephalitis virus, and St. Louis encephalitis virus (1). The natural transmission cycle of WNV is between birds and mosquitoes, primarily the Culex species; however, it can cause incidental infections in humans. Since the outbreak of the more pathogenic WNVNY99 strain in New York in 1999 (2), WNV has emerged as a major cause of arboviral encephalitis in the United States (3). WNV strains can be divided into two distinct lineages, lineage 1 and lineage 2. Lineage 1 includes both WNVNY99 an