title: Cholesterol shuttling is important for RNA replication of coxsackievirus B3 and encephalomyocarditis virus.
abstract: Picornaviruses are a family of positive-strand RNA viruses that includes important human and animal pathogens. Upon infection, picornaviruses induce an extensive remodelling of host cell membranes into replication organelles (ROs), which is critical for replication. Membrane lipids and lipid remodelling processes are at the base of RO formation, yet their involvement remains largely obscure. Recently, phosphatidylinositol-4-phosphate was the first lipid discovered to be important for the replication of a number of picornaviruses. Here, we investigate the role of the lipid cholesterol in picornavirus replication. We show that two picornaviruses from distinct genera that rely on different host factors for replication, namely the enterovirus coxsackievirus B3 (CVB3) and the cardiovirus encephalomyocarditis virus (EMCV), both recruited cholesterol to their ROs. Although CVB3 and EMCV both required cholesterol for efficient genome replication, the viruses appeared to rely on different cellular cholesterol pools. Treatments that altered the distribution of endosomal cholesterol inhibited replication of both CVB3 and EMCV, showing the importance of endosomal cholesterol shuttling for the replication of these viruses. Summarizing, we here demonstrate the importance of cholesterol homeostasis for efficient replication of CVB3 and EMCV.
authors: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Lucian
authors: L
authors: Albulescu
authors: Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Richard
authors: R
authors: Wubbolts
authors: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Frank J M
authors: FJ
authors: van Kuppeveld
authors: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Jeroen R P M
authors: JR
authors: Strating
mesh_terms: D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002784:Cholesterol / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000502:physiology*; D029822:Enterovirus B, Human / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015388:Organelles / Q000378:metabolism / Q000821:virology; D012367:RNA, Viral / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D002784:Cholesterol