ATF6 signaling is required for efficient west nile virus replication by promoting cell survival and inhibition of innate immune responses

Abstract

West Nile virus strain Kunjin (WNVKUN) is an enveloped, positive-sense RNA virus within the virus family Flaviviridae. Many flaviviruses have been shown to manipulate multiple signaling pathways, including autophagic, innate immune, and stress responses, in order to benefit replication. In particular, we have demonstrated that WNVKUN regulates the unfolded protein response (UPR), skewing the downstream effectors toward chaperone expression and Xbp-1 activation while preventing PERKmediated translation attenuation and C/EBP homologous protein (CHOP) upregulation. WNVKUN-regulated UPR signaling can then be hijacked in order to affect type I interferon (IFN) responses, preventing IFN-mediated S..