title: Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction.
abstract: Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell. Importantly, we find that transmitted founder HIV-1, which establishes de novo infections, is uniquely resistant to the antiviral activity of IFITMs. However, viral sensitivity to IFITMs, particularly IFITM2 and IFITM3, increases over the first 6 months of infection, primarily as a result of neutralizing antibody escape mutations. Additionally, the ability to evade IFITM restriction contributes to the different interferon sensitivities of transmitted founder and chronic viruses. Together, these data indicate that IFITMs constitute an important barrier to HIV-1 transmission and that escape from adaptive immune responses exposes the virus to antiviral restriction.
authors.affiliation: Department of Infectious Diseases, King's College London Faculty of Life Sciences and Medicine, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Toshana L
authors.initials: TL
authors.lastname: Foster
authors.affiliation: Department of Infectious Diseases, King's College London Faculty of Life Sciences and Medicine, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Wilson
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Shilpa S
authors.initials: SS
authors.lastname: Iyer
authors.affiliation: Department of Infectious Diseases, King's College London Faculty of Life Sciences and Medicine, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Coss
authors.affiliation: Department of Infectious Diseases, King's College London Faculty of Life Sciences and Medicine, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Doores
authors.affiliation: Wellcome Trust Sanger Centre, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Smith
authors.affiliation: Wellcome Trust Sanger Centre, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.affiliation: Centre de Recherche du CHUM and Department of Microbiology, Infection, and Immunology, Université de Montréal, Montréal, QC H3T 1J4, Canada.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX1 2JD, UK.
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Department of Infectious Diseases, King's College London Faculty of Life Sciences and Medicine, Guy's Hospital, London SE1 9RT, UK. Electronic address: stuart.neil@kcl.ac.uk.
authors.forename: Stuart J D
authors.initials: SJD
authors.lastname: Neil
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D000943:Antigens, Differentiation / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D056189:Viral Tropism; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; C062010:leu-13 antigen
keywords: CD4; HIV-1; IFITM; antiviral restriction; co-receptor; escape; neutralization; transmitted founder virus; type 1 interferon