title: Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses.
abstract: Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV. Mechanistic analysis indicated that depletion of cellular cholesterol reduced cell surface accumulation of envelope glycoproteins and association of viral matrix and nucleocapsids with raft membrane, which resulted in impaired virus budding and release from the cells. These results indicate that cellular cholesterol is required for assembly and formation of type 1 parainfluenza viruses and suggest that cholesterol could be an attractive target for antiviral agents against hPIV1.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Shringkhala
authors.initials: S
authors.lastname: Bajimaya
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Tünde
authors.initials: T
authors.lastname: Frankl
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Bryk
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Ward
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: toru_takimoto@urmc.rochester.edu.
authors.forename: Toru
authors.initials: T
authors.lastname: Takimoto
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D010222:Parainfluenza Virus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018184:Paramyxoviridae Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D021381:Protein Transport; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D019065:Virus Assembly / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D014764:Viral Proteins; D002784:Cholesterol
keywords: Antiviral therapy; Assembly; Cholesterol; Lipid rafts; Type I parainfluenza virus