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The human antibody response to the immunodominant HIV-1 glycoprotein complex and its subsequent evolution with disease progression has been the focus of considerable investigation in recent years. However, the basis for the human antibody responses to HIV-1 remains unclear, especially the molecular basis of the differences in neutralization sensitivities of HIV-1 among infected individuals. In this study we have utilized monoclonal antibodies (MAbs) to define the relative sensitivity of the V3 loop to HIV-1 neutralization and to determine whether the V3 loop of HIV-1 envelopes can bind to MAbs even when neutralization resistance occurs. We have found that the V3 loop of the HIV-1, in addition to neutralization by human or murine anti-HIV-1 MAbs, can bind to human and murine MAbs specific for the neutralization epitopes of the V3 loop. We also have found that in vitro evolution of two HIV-1 isolates with different neutralization susceptibility resulted in detectable changes in the V3 loop structure of the envelope, which correlated with decreased binding to the human MAbs. These results provide an explanation for the evolution of neutralization sensitivity to HIV-1 with disease progression and provide a functional basis for the epitope specificities of HIV-1 antibodies.Q:
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