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

Autor: S Gnanakaran, Tanmoy Bhattacharya, Marcus Daniels, Brandon F Keele, Peter T Hraber, Alan S Lapedes, Tongye Shen, Brian Gaschen, Mohan Krishnamoorthy, Hui Li, Julie M Decker, Jesus F Salazar-Gonzalez, Shuyi Wang, Chunlai Jiang, Feng Gao, Ronald Swanstrom, Jeffrey A Anderson, Li-Hua Ping, Myron S Cohen, Martin Markowitz, Paul A Goepfert, Michael S Saag, Joseph J Eron, Charles B Hicks, William A Blattner, Georgia D Tomaras, Mohammed Asmal, Norman L Letvin, Peter B Gilbert, Allan C Decamp, Craig A Magaret, William R Schief, Yih-En Andrew Ban, Ming Zhang, Kelly A Soderberg, Joseph G Sodroski, Barton F Haynes, George M Shaw, Beatrice H Hahn, Bette Korber
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS Pathogens, Vol 7, Iss 9, p e1002209 (2011)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1002209
Popis: 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.
Databáze: Directory of Open Access Journals
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