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

• Published in: The Journal of experimental medicine Vol. 208; no. 11; pp. 2237 - 2249
• Main Authors: Liao, Hua-Xin, Chen, Xi, Munshaw, Supriya, Zhang, Ruijun, Marshall, Dawn J., Vandergrift, Nathan, Whitesides, John F., Lu, Xiaozhi, Yu, Jae-Sung, Hwang, Kwan-Ki, Gao, Feng, Markowitz, Martin, Heath, Sonya L., Bar, Katharine J., Goepfert, Paul A., Montefiori, David C., Shaw, George C., Alam, S. Munir, Margolis, David M., Denny, Thomas N., Boyd, Scott D., Marshal, Eleanor, Egholm, Michael, Simen, Birgitte B., Hanczaruk, Bozena, Fire, Andrew Z., Voss, Gerald, Kelsoe, Garnett, Tomaras, Georgia D., Moody, M. Anthony, Kepler, Thomas B., Haynes, Barton F.
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 24.10.2011
• Subjects: Adult; Cell Lineage; Female; HIV Antibodies - classification; HIV Antibodies - genetics; HIV Antibodies - immunology; HIV Envelope Protein gp41 - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Male; Mutation; Phylogeny; Plasma Cells - immunology; Plasma Cells - virology; Sequence Analysis, DNA; Viral Load; Viremia - immunology
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20110363

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.