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We previously demonstrated that ASMase-deficient mice are more susceptible to fatal SINV encephalomyelitis, with increased viral replication, spread, and neuronal death. To determine the mechanisms by which ASMase deficiency enhances SINV replication, we compared NPD-A fibroblasts (NPAF) to normal human fibroblasts (NHF). NPAF accumulated cholesterol- and sphingolipid-rich late endosomes\/lysosomes in the perinuclear region. SINV replication was faster and reached higher titer in NPAF than in NHF, and NPAF died more quickly. SINV RNA and protein synthesis was greater in NHF than in NPAF, but virions budding from NPAF were 26 times more infectious and were regular dense particles whereas virions from NHF were larger particles containing substantial amounts of CD63. Cellular regulation of alphavirus morphogenesis is a previously unrecognized mechanism for control of virus replication and spread.<\/jats:p>","DOI":"10.1073\/pnas.0808720105","type":"journal-article","created":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T21:26:37Z","timestamp":1223587597000},"page":"16326-16331","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Effect of host cell lipid metabolism on alphavirus replication, virion morphogenesis, and infectivity"],"prefix":"10.1073","volume":"105","author":[{"given":"Ching G.","family":"Ng","sequence":"first","affiliation":[{"name":"*W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Coppens","sequence":"additional","affiliation":[{"name":"*W. 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