Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
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.
Liao, H-X; Chen, X; Munshaw, S; Zhang, R; Marshall, DJ; Vandergrift, N; Whitesides, JF; Lu, X; Yu, J-S; Hwang, K-K; Gao, F; Markowitz, M; Heath, SL; Bar, KJ; Goepfert, PA; Montefiori, DC; Shaw, GC; Alam, SM; Margolis, DM; Denny, TN; Boyd, SD; Marshal, E; Egholm, M; Simen, BB; Hanczaruk, B; Fire, AZ; Voss, G; Kelsoe, G; Tomaras, GD; Moody, MA; Kepler, TB; Haynes, BF
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