Effect of host cell lipid metabolism on alphavirus replication, virion morphogenesis, and infectivity

• DOI: 10.1073/pnas.0808720105
• Publication Date: 2008-10-10T01:26:37Z
• Authors: Ching G. Ng; Isabelle Coppens; Dhanasekaran Govi...; John Pisciotta; Vladimir Shulaev; Diane E. Griffin
• Keywords: Alphavirus infection; Sindbis virus; Acid sphingomyelinase

The alphavirus Sindbis virus (SINV) causes encephalomyelitis in mice. Lipid-containing membranes, particularly cholesterol and sphingomyelin (SM), play important roles entry, RNA replication, glycoprotein transport, budding. Levels of SM are regulated by sphingomyelinases (SMases). Acid SMase (ASMase) deficiency results the lipid storage disease type A Niemann-Pick (NPD-A), mimicked mice interruption ASMase gene. We previously demonstrated that ASMase-deficient more susceptible to fatal SINV encephalomyelitis, with increased viral spread, neuronal death. To determine mechanisms which enhances we compared NPD-A fibroblasts (NPAF) normal human (NHF). NPAF accumulated cholesterol- sphingolipid-rich late endosomes/lysosomes perinuclear region. replication was faster reached higher titer than NHF, died quickly. protein synthesis greater NHF NPAF, but virions budding from were 26 times infectious regular dense particles whereas larger containing substantial amounts CD63. Cellular regulation morphogenesis is a unrecognized mechanism for control spread.