Phylogenetic analysis of WNV strains reveals the presence of two closely related but nonetheless distinct virus groups termed lineage I and lineage II ( 6). The natural transmission cycle of WNV involves mosquitoes and birds, with humans and other mammals as incidental hosts ( 8, 27). West Nile virus (WNV) is an arthropod-borne virus classified in the Japanese encephalitis antigenic complex of the family Flaviviridae ( 9, 20, 32). This suggests a multifaceted role for envelope N-linked glycosylation in WNV biology and tropism. Thus, glycosylation of WNV prM and E proteins can affect the efficiency of virus release and infection in a manner that is cell type and perhaps species dependent. Those particles lacking glycosylation on the E protein were modestly more infectious per genome copy on BHK-21 and QT6 cells, while this absence greatly enhanced the infection of C6/36 cells. RVPs or virions bearing combinations of glycosylated and nonglycosylated forms of prM and E could infect mammalian, avian, and mosquito cells (BHK-21, QT6, and C6/36, respectively). Similar results were obtained in the context of either reporter virus particles (RVPs) or infectious lineage II WNV. Addition of the E protein glycosylation site in a lineage II strain that lacked this site increased SVP production. Removing the prM glycosylation site in a lineage I or II strain decreased SVP release, as did removal of the glycosylation site in a lineage I E protein. Similar to other flaviviruses, expression of WNV prM and E resulted in the release of subviral particles (SVPs). Therefore, we examined the impact of prM and E glycosylation on WNV assembly and infectivity. The presence of N-linked glycosylation on flavivirus E proteins has been linked to virus production, pH sensitivity, and neuroinvasiveness. While the prM protein of all WNV strains contains a single N-linked glycosylation site, not all strains contain an N-linked site in the E protein. West Nile virus (WNV) encodes two envelope proteins, premembrane (prM) and envelope (E).
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