Host sphingomyelin increases West Nile virus infection in vivo.

摘要: Flaviviruses, such as the dengue virus and West Nile (WNV), are arthropod-borne viruses that represent a global health problem. The flavivirus lifecycle is intimately connected to cellular lipids. Among lipids co-opted by flaviviruses, we have focused on SM, an important component of membranes particularly enriched in nervous system. After infection with neurotropic WNV, mice deficient acid sphingomyelinase (ASM), which accumulate high levels SM their tissues, displayed exacerbated infection. In addition, WNV multiplication was enhanced cells from human patients Niemann-Pick type A, disease caused deficiency ASM activity resulting accumulation. Furthermore, addition cultured also increased infection, whereas treatment pharmacological inhibitors synthesis reduced Confocal microscopy analyses confirmed association viral replication sites within infected cells. Our results unveil metabolism regulates vivo propose suitable target for antiviral design against WNV.