title: Enteroviruses harness the cellular endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication.
abstract: 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.
authors.affiliation: Laboratory of Host-Pathogen Dynamics, Rutgers University, Newark, NJ 07102, USA.
authors.forename: Olha
authors.initials: O
authors.lastname: Ilnytska
authors.forename: Marianita
authors.initials: M
authors.lastname: Santiana
authors.forename: Nai-Yun
authors.initials: NY
authors.lastname: Hsu
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Du
authors.forename: Ying-Han
authors.initials: YH
authors.lastname: Chen
authors.forename: Ekaterina G
authors.initials: EG
authors.lastname: Viktorova
authors.forename: Georgy
authors.initials: G
authors.lastname: Belov
authors.forename: Anita
authors.initials: A
authors.lastname: Brinker
authors.forename: Judith
authors.initials: J
authors.lastname: Storch
authors.forename: Christopher
authors.initials: C
authors.lastname: Moore
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Dixon
authors.forename: Nihal
authors.initials: N
authors.lastname: Altan-Bonnet
mesh_terms: D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002784:Cholesterol / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D004770:Enterovirus / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D014779:Virus Replication
chemical_list: D002784:Cholesterol
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