DEVELOPMENT OF A NEUTRALIZING ANTIBODY-RESPONSE DURING ACUTE PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND THE EMERGENCE OF ANTIGENIC VARIANTS

We monitored the primary humoral response to human immunodeficiency vi rus type 1 infection and showed that, in addition to antibodies to p24 and gp41, antigens which form the basis of most diagnostic assays, th e response included a significant antibody response directed to the gp 120 region of the infecting viral quasispecies. When tested in a recom binant virus neutralization assay, these antibodies were capable of in hibiting viral growth. We found the primary viral quasispecies to sole ly utilize the CCR-5 chemokine receptor; however, recombinant viruses differed in their cytopathology and in their sensitivity to beta-chemo kine inhibition of viral growth. Sequence analysis of the gp120 open r eading frames showed that amino acid changes in the C1 (D-->G at posit ion 62) and C4 (V-->A at position 430) regions accounted for the pheno typic differences. These data demonstrate that early in infection, pol ymorphism exists in envelope glycoprotein coreceptor interactions and imply that therapeutic strategies targeted at this step in the viral l ife cycle may lead to rapid resistance.