title: The major cellular sterol regulatory pathway is required for Andes virus infection.
abstract: The Bunyaviridae comprise a large family of RNA viruses with worldwide distribution and includes the pathogenic New World hantavirus, Andes virus (ANDV). Host factors needed for hantavirus entry remain largely enigmatic and therapeutics are unavailable. To identify cellular requirements for ANDV infection, we performed two parallel genetic screens. Analysis of a large library of insertionally mutagenized human haploid cells and a siRNA genomic screen converged on components (SREBP-2, SCAP, S1P and S2P) of the sterol regulatory pathway as critically important for infection by ANDV. The significance of this pathway was confirmed using functionally deficient cells, TALEN-mediated gene disruption, RNA interference and pharmacologic inhibition. Disruption of sterol regulatory complex function impaired ANDV internalization without affecting virus binding. Pharmacologic manipulation of cholesterol levels demonstrated that ANDV entry is sensitive to changes in cellular cholesterol and raises the possibility that clinically approved regulators of sterol synthesis may prove useful for combating ANDV infection.
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Josiah
authors: J
authors: Petersen
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Mary Jane
authors: MJ
authors: Drake
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Emily A
authors: EA
authors: Bruce
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Amber M
authors: AM
authors: Riblett
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Chukwuka A
authors: CA
authors: Didigu
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Craig B
authors: CB
authors: Wilen
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Nirav
authors: N
authors: Malani
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Frances
authors: F
authors: Male
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Fang-Hua
authors: FH
authors: Lee
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Frederic D
authors: FD
authors: Bushman
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Sara
authors: S
authors: Cherry
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America ; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors: Robert W
authors: RW
authors: Doms
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Paul
authors: P
authors: Bates
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Kenneth
authors: K
authors: Briley
mesh_terms: D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005434:Flow Cytometry; D006476:Orthohantavirus / Q000472:pathogenicity*; D018778:Hantavirus Infections / Q000378:metabolism*; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013261:Sterols / Q000378:metabolism; D014161:Transduction, Genetic; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology
chemical_list: D013261:Sterols; D002784:Cholesterol