title: Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection.
abstract: Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .|3 Department of Biological Sciences, University of Botswana , Gaborone, Botswana .|4 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Raabya
authors.initials: R
authors.lastname: Rossenkhan
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Iain J
authors.initials: IJ
authors.lastname: MacLeod
authors.affiliation: 5 Faculty of Health Sciences, Simon Fraser University , Burnaby, Canada .|6 British Columbia Centre for Excellence in HIV/AIDS , Vancouver, Canada .
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.affiliation: 4 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Magaret
authors.affiliation: 3 Department of Biological Sciences, University of Botswana , Gaborone, Botswana .
authors.forename: Theresa K
authors.initials: TK
authors.lastname: Sebunya
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Rosemary
authors.initials: R
authors.lastname: Musonda
authors.affiliation: 3 Department of Biological Sciences, University of Botswana , Gaborone, Botswana .
authors.forename: Berhanu A
authors.initials: BA
authors.lastname: Gashe
authors.affiliation: 4 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: Vlad
authors.initials: V
authors.lastname: Novitsky
authors.affiliation: 1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.|2 Botswana Harvard AIDS Institute , Gaborone, Botswana .
authors.forename: M
authors.initials: M
authors.lastname: Essex
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000939:Epitopes / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012641:Selection, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D000086082:Viroporin Proteins
chemical_list: D000939:Epitopes; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; C514912:vpr protein, Human immunodeficiency virus 1; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: CTL epitope; HIV transmission; Vif; Vpr; Vpu; accessory genes; evolution