Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.

Abstract

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.

• Authors: Hua-Xin Liao, Xi Chen, Supriya Munshaw, Ruijun Zhang, Dawn J Marshall, Nathan Vandergrift, John F Whitesides, Xiaozhi Lu, Jae-Sung Yu, Kwan-Ki Hwang, Feng Gao, Martin Markowitz, Sonya L Heath, Katharine J Bar, Paul A Goepfert, David C Montefiori, George C Shaw, S Munir Alam, David M Margolis, Thomas N Denny, Scott D Boyd, Eleanor Marshal, Michael Egholm, Birgitte B Simen, Bozena Hanczaruk, Andrew Z Fire, Gerald Voss, Garnett Kelsoe, Georgia D Tomaras, M Anthony Moody, Thomas B Kepler, Barton F Haynes
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 208 Issue 11 Pg. 2237-49 (Oct 24 2011) ISSN: 1540-9538 [Electronic] United States
• PMID: 21987658 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HIV Antibodies
• HIV Envelope Protein gp41

Topics

• Adult
• Cell Lineage
• Female
• HIV Antibodies (classification, genetics, immunology)
• HIV Envelope Protein gp41 (immunology)
• HIV-1 (immunology)
• Humans
• Male
• Mutation
• Phylogeny
• Plasma Cells (immunology, virology)
• Sequence Analysis, DNA
• Viral Load
• Viremia (immunology)