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Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.

Publication ,  Journal Article
Gnanakaran, S; Bhattacharya, T; Daniels, M; Keele, BF; Hraber, PT; Lapedes, AS; Shen, T; Gaschen, B; Krishnamoorthy, M; Li, H; Decker, JM ...
Published in: PLoS Pathog
September 2011

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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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

September 2011

Volume

7

Issue

9

Start / End Page

e1002209

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Retrospective Studies
  • Receptors, CCR5
  • Protein Sorting Signals
  • Mutation, Missense
  • HIV-1
  • HIV Infections
  • Glycosylation
  • Gene Expression Regulation, Viral
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gnanakaran, S., Bhattacharya, T., Daniels, M., Keele, B. F., Hraber, P. T., Lapedes, A. S., … Korber, B. (2011). Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. PLoS Pathog, 7(9), e1002209. https://doi.org/10.1371/journal.ppat.1002209
Gnanakaran, S., Tanmoy Bhattacharya, Marcus Daniels, Brandon F. Keele, Peter T. Hraber, Alan S. Lapedes, Tongye Shen, et al. “Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.PLoS Pathog 7, no. 9 (September 2011): e1002209. https://doi.org/10.1371/journal.ppat.1002209.
Gnanakaran S, Bhattacharya T, Daniels M, Keele BF, Hraber PT, Lapedes AS, et al. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. PLoS Pathog. 2011 Sep;7(9):e1002209.
Gnanakaran, S., et al. “Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.PLoS Pathog, vol. 7, no. 9, Sept. 2011, p. e1002209. Pubmed, doi:10.1371/journal.ppat.1002209.
Gnanakaran S, Bhattacharya T, Daniels M, Keele BF, Hraber PT, Lapedes AS, Shen T, Gaschen B, Krishnamoorthy M, Li H, Decker JM, Salazar-Gonzalez JF, Wang S, Jiang C, Gao F, Swanstrom R, Anderson JA, Ping L-H, Cohen MS, Markowitz M, Goepfert PA, Saag MS, Eron JJ, Hicks CB, Blattner WA, Tomaras GD, Asmal M, Letvin NL, Gilbert PB, Decamp AC, Magaret CA, Schief WR, Ban Y-EA, Zhang M, Soderberg KA, Sodroski JG, Haynes BF, Shaw GM, Hahn BH, Korber B. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. PLoS Pathog. 2011 Sep;7(9):e1002209.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

September 2011

Volume

7

Issue

9

Start / End Page

e1002209

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Retrospective Studies
  • Receptors, CCR5
  • Protein Sorting Signals
  • Mutation, Missense
  • HIV-1
  • HIV Infections
  • Glycosylation
  • Gene Expression Regulation, Viral