title: HIV-1 mutates to evade IFITM1 restriction.
abstract: Interferon-induced transmembrane (IFITM) proteins inhibit the infection of a wide range of viruses including human immunodeficiency virus type 1 (HIV-1). At present, little is known about how viruses overcome IFITM restriction. In this study, we have utilized HIV-1 as a model and selected IFITM1-resistant viruses after multiple passages of HIV-1 in IFITM1-expressing SupT1 cells. Sequencing the entire viral genome revealed several mutations in the vpu and envelope genes, among which mutations Vpu34 and EnvG367E together enable efficient HIV-1 replication in IFITM1-expressing cells. Vpu34 introduces a stop codon at amino acid position 35 of Vpu, whereas EnvG367E changes the G367 residue at the CD4-binding site of gp120. These two mutations do not appear to overcome the downregulation of viral p24 expression caused by IFITM1, but rather enhance HIV-1 replication by promoting cell-to-cell virus transmission. Altogether, our data demonstrate that HIV-1 can mutate to evade IFITM1 restriction by increasing cell-to-cell transmission.
authors.affiliation: Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada H3T 1E2; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada H3A 2B4.
authors.forename: Shilei
authors.initials: S
authors.lastname: Ding
authors.affiliation: Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada H3T 1E2.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Molecular Microbiology & Immunology, School of Medicine, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211-7310, USA. Electronic address: liushan@missouri.edu.
authors.forename: Shan-Lu
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada H3T 1E2; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada H3A 2B4; Department of Medicine, McGill University, Montreal, QC, Canada H3A 2B4. Electronic address: chen.liang@mcgill.ca.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
mesh_terms: D000943:Antigens, Differentiation / Q000276:immunology*; D002460:Cell Line; D004252:DNA Mutational Analysis; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics; D006801:Humans; D057131:Immune Evasion; D009154:Mutation; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D000086082:Viroporin Proteins
chemical_list: D000943:Antigens, Differentiation; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C062010:leu-13 antigen; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: Cell-to-cell transmission; Escape mutations; HIV-1; IFITM1
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