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

M. A. Moody; Nathan Alexander Vandergrift; H X  Liao; Xi Chen; Supriya Munshaw; Ruijun Zhang; Dawn J Marshall; Nathan Alexander 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

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

Liao, H.-X., Chen, X., Munshaw, S., Zhang, R., Marshall, D. J., Vandergrift, N. A., Whitesides, J. F., Lu, X., Yu, J.-S., Hwang, K.-K., Gao, F., Markowitz, M., Heath, S. L., Bar, K. J., Goepfert, P. A., Montefiori, D. C., Shaw, G. C., Alam, S. M., Margolis, D. M., ... Haynes, B. F. (2011). Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. Journal of Experimental Medicine, 208(11), 2237-2249. https://doi.org/10.1084/jem.20110363

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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.