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Enteroviruses Harness the Cellular Endocytic Machinery to Remodel the Host Cell Cholesterol Landscape for Effective Viral Replication

2013; Cell Press; Volume: 14; Issue: 3 Linguagem: Inglês

10.1016/j.chom.2013.08.002

1934-6069

Olga Ilnytska, Marianita Santiana, Nai-Yun Hsu, Wenli Du, Ying-Han Chen, Ekaterina G. Viktorova, George A. Belov, Anita Brinker, Judith Storch, Christopher Moore, Joseph L. Dixon, Nihal Altan‐Bonnet,

Trypanosoma species research and implications

Cholesterol is a critical component of cellular membranes, regulating assembly and function of membrane-based protein/lipid complexes. Many RNA viruses, including enteroviruses, remodel host membranes to generate organelles with unique lipid blueprints on which they assemble replication complexes and synthesize viral RNA. Here we find that clathrin-mediated endocytosis (CME) is harnessed by enteroviruses to traffic cholesterol from the plasma membrane (PM) and extracellular medium to replication organelles, where cholesterol then regulates viral polyprotein processing and facilitates genome synthesis. When CME is disrupted, cellular cholesterol pools are instead stored in lipid droplets, cholesterol cannot be trafficked to replication organelles, and replication is inhibited. In contrast, replication is stimulated in cholesterol-elevated cells like those lacking caveolins or those from Niemann-Pick disease patients. Our findings indicate cholesterol as a critical determinant for enteroviral replication and outline roles for the endocytic machinery in both the enteroviral life cycle and host cell cholesterol homeostasis.