Critical role of lipid rafts in virus entry and activation of phosphoinositide 3′ kinase/Akt signaling during early stages of Japanese encephalitis virus infection in neural stem/progenitor cells

作者: Sulagna Das , Swarupa Chakraborty , Anirban Basu

DOI: 10.1111/J.1471-4159.2010.06951.X

关键词: Membrane fluidityLipid raftViral entryVirologyNeurotropic virusBiologyClathrinEndocytosisFlavivirusProgenitor cell

摘要: Japanese encephalitis virus (JEV), the leading cause of acute in South-East Asia is a neurotropic infecting various CNS cell types. Most Flaviviruses including JEV get internalised into cells by receptor-mediated endocytosis, which involve clathrin and membrane cholesterol. The cholesterol-enriched microdomains referred to as lipid rafts act portals for entry number enveloped viruses, Flavivirus. However, precise role played internalisation neural stem still unknown. We have established stem/progenitor C17.2 line models productive infection. Increase fluidity clustering viral envelope proteins was observed early time points Localisation non-structural at later infection stages also observed. Co-localisation glycoprotein with Cholera toxin B confirmed that occurs lipid-raft dependent manner. Though raft dependent, however, there requirement functional during endocytosis inside cells. Besides entry, signalling platforms Src tyrosine kinases result activation phosphoinositide 3'-kinase/Akt Disruption formation cholesterol depletion using Methyl β-cyclodextrin, reduced RNA levels production infectious particles well impaired initial Overall, our results implicate importance host life cycle, besides maintaining survival

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