title: Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.
abstract: Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.
authors: Theoretical Biology, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
authors: S
authors: S
authors: Gnanakaran
authors: Tanmoy
authors: T
authors: Bhattacharya
authors: Marcus
authors: M
authors: Daniels
authors: Brandon F
authors: BF
authors: Keele
authors: Peter T
authors: PT
authors: Hraber
authors: Alan S
authors: AS
authors: Lapedes
authors: Tongye
authors: T
authors: Shen
authors: Brian
authors: B
authors: Gaschen
authors: Mohan
authors: M
authors: Krishnamoorthy
authors: Hui
authors: H
authors: Li
authors: Julie M
authors: JM
authors: Decker
authors: Jesus F
authors: JF
authors: Salazar-Gonzalez
authors: Shuyi
authors: S
authors: Wang
authors: Chunlai
authors: C
authors: Jiang
authors: Feng
authors: F
authors: Gao
authors: Ronald
authors: R
authors: Swanstrom
authors: Jeffrey A
authors: JA
authors: Anderson
authors: Li-Hua
authors: LH
authors: Ping
authors: Myron S
authors: MS
authors: Cohen
authors: Martin
authors: M
authors: Markowitz
authors: Paul A
authors: PA
authors: Goepfert
authors: Michael S
authors: MS
authors: Saag
authors: Joseph J
authors: JJ
authors: Eron
authors: Charles B
authors: CB
authors: Hicks
authors: William A
authors: WA
authors: Blattner
authors: Georgia D
authors: GD
authors: Tomaras
authors: Mohammed
authors: M
authors: Asmal
authors: Norman L
authors: NL
authors: Letvin
authors: Peter B
authors: PB
authors: Gilbert
authors: Allan C
authors: AC
authors: Decamp
authors: Craig A
authors: CA
authors: Magaret
authors: William R
authors: WR
authors: Schief
authors: Yih-En Andrew
authors: YE
authors: Ban
authors: Ming
authors: M
authors: Zhang
authors: Kelly A
authors: KA
authors: Soderberg
authors: Joseph G
authors: JG
authors: Sodroski
authors: Barton F
authors: BF
authors: Haynes
authors: George M
authors: GM
authors: Shaw
authors: Beatrice H
authors: BH
authors: Hahn
authors: Bette
authors: B
authors: Korber
mesh_terms: D056704:Adaptive Immunity; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000914:Antibodies, Viral / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006031:Glycosylation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D020125:Mutation, Missense; D021382:Protein Sorting Signals / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D054299:env Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000914:Antibodies, Viral; D015704:CD4 Antigens; D021382:Protein Sorting Signals; D019713:Receptors, CCR5; D054299:env Gene Products, Human Immunodeficiency Virus