title: IFITM-2 and IFITM-3 but not IFITM-1 restrict Rift Valley fever virus.
abstract: We show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the Bunyaviridae family, including Rift Valley fever virus (RVFV), La Crosse virus, Andes virus, and Hantaan virus, all of which can cause severe disease in humans and animals. We found that RVFV was restricted by IFITM-2 and -3 but not by IFITM-1, whereas the remaining viruses were equally restricted by all IFITMs. Indeed, at low doses of alpha interferon (IFN-α), IFITM-2 and -3 mediated more than half of the antiviral activity of IFN-α against RVFV. IFITM-2 and -3 restricted RVFV infection mostly by preventing virus membrane fusion with endosomes, while they had no effect on virion attachment to cells, endocytosis, or viral replication kinetics. We found that large fractions of IFITM-2 and IFITM-3 occupy vesicular compartments that are distinct from the vesicles coated by IFITM-1. In addition, although overexpression of all IFITMs expanded vesicular and acidified compartments within cells, there were marked phenotypic differences among the vesicular compartments occupied by IFITMs. Collectively, our data provide new insights into the possible mechanisms by which the IFITM family members restrict distinct viruses.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland USA.
authors.forename: Rajini
authors.initials: R
authors.lastname: Mudhasani
authors.forename: Julie P
authors.initials: JP
authors.lastname: Tran
authors.forename: Cary
authors.initials: C
authors.lastname: Retterer
authors.forename: Sheli R
authors.initials: SR
authors.lastname: Radoshitzky
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Kota
authors.forename: Louis A
authors.initials: LA
authors.lastname: Altamura
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Smith
authors.forename: Beverly Z
authors.initials: BZ
authors.lastname: Packard
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.forename: Julie
authors.initials: J
authors.lastname: Costantino
authors.forename: Aura R
authors.initials: AR
authors.lastname: Garrison
authors.forename: Connie S
authors.initials: CS
authors.lastname: Schmaljohn
authors.forename: I-Chueh
authors.initials: IC
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology*; D002460:Cell Line; D018063:Hantaan virus / Q000276:immunology / Q000502:physiology; D006476:Orthohantavirus / Q000276:immunology / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D018062:La Crosse virus / Q000276:immunology / Q000502:physiology; D008565:Membrane Proteins / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*; D012296:Rift Valley fever virus / Q000276:immunology* / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D000943:Antigens, Differentiation; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D016898:Interferon-alpha; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C062010:leu-13 antigen