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Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections

  1. Author:
    Gnanakaran, S.
    Bhattacharya, T.
    Daniels, M.
    Keele, B. F.
    Hraber, P. T.
    Lapedes, A. S.
    Shen, T. Y.
    Gaschen, B.
    Krishnamoorthy, M.
    Li, H.
    Decker, J. M.
    Salazar-Gonzalez, J. F.
    Wang, S. Y.
    Jiang, C. L.
    Gao, F.
    Swanstrom, R.
    Anderson, J. A.
    Ping, L. H.
    Cohen, M. S.
    Markowitz, M.
    Goepfert, P. A.
    Saag, M. S.
    Eron, J. J.
    Hicks, C. B.
    Blattner, W. A.
    Tomaras, G. D.
    Asmal, M.
    Letvin, N. L.
    Gilbert, P. B.
    DeCamp, A. C.
    Magaret, C. A.
    Schief, W. R.
    Ban, Y. E. A.
    Zhang, M.
    Soderberg, K. A.
    Sodroski, J. G.
    Haynes, B. F.
    Shaw, G. M.
    Hahn, B. H.
    Korber, B.

  2. Author Address

    [Gnanakaran, S; Bhattacharya, T; Daniels, M; Hraber, PT; Lapedes, AS; Shen, TY; Gaschen, B; Krishnamoorthy, M; Zhang, M; Korber, B] Los Alamos Natl Lab, Los Alamos, NM USA. [Bhattacharya, T; Korber, B] Santa Fe Inst, Santa Fe, NM 87501 USA. [Keele, BF] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Keele, BF; Li, H; Decker, JM; Salazar-Gonzalez, JF; Wang, SY; Goepfert, PA; Saag, MS; Shaw, GM; Hahn, BH] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Keele, BF; Li, H; Decker, JM; Salazar-Gonzalez, JF; Wang, SY; Goepfert, PA; Saag, MS; Shaw, GM; Hahn, BH] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Shen, TY] Univ Tennessee, Ctr Biophys Mol, Knoxville, TN USA. [Shen, TY] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN USA. [Jiang, CL] Jilin Univ, Sch Life Sci, Natl Engn Lab AIDS Vaccine, Changchun 130023, Peoples R China. [Jiang, CL; Gao, F; Hicks, CB; Tomaras, GD; Soderberg, KA; Haynes, BF] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Jiang, CL; Gao, F; Hicks, CB; Tomaras, GD; Soderberg, KA; Haynes, BF] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Jiang, CL; Gao, F; Hicks, CB; Tomaras, GD; Soderberg, KA; Haynes, BF] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA. [Swanstrom, R; Anderson, JA; Ping, LH; Cohen, MS; Eron, JJ] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. [Swanstrom, R; Anderson, JA; Ping, LH; Cohen, MS; Eron, JJ] Univ N Carolina, Div Infect Dis, Ctr AIDS Res, Chapel Hill, NC USA. [Markowitz, M] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. [Blattner, WA] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Asmal, M; Letvin, NL] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Letvin, NL] Harvard Univ, Sch Med, Dept Med, Div Viral Pathogenesis, Boston, MA USA. [Gilbert, PB; DeCamp, AC; Magaret, CA] Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Div, Seattle, WA 98104 USA. [Schief, WR; Ban, YEA] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Ban, YEA] Arzeda Corp, Seattle, WA USA. [Zhang, M] Univ Georgia, Coll Publ Hlth, Dept Epidemiol & Biostat, Athens, GA 30602 USA. [Sodroski, JG] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.;Gnanakaran, S (reprint author), Los Alamos Natl Lab, Los Alamos, NM USA;btk@lanl.gov
    1. Year: 2011
    2. Date: Sep
  2. Journal: Plos Pathogens
    1. 7
    2. 9
    3. Pages: 19
  4. Type of Article: Article
  5. Article Number: e1002209
  6. ISSN: 1553-7366
  1. 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.

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External Sources

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  2. DOI: 10.1371/journal.ppat.1002209
  3. View record in Web of Science®
  4. WOS: 000295409000017

Library Notes

  1. Fiscal Year: FY2011-2012
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