IMMUNE ESCAPE BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM NEUTRALIZING ANTIBODIES - EVIDENCE FOR MULTIPLE PATHWAYS

Sera from many HIV-1-infected individuals contain broadly reactive, sp ecific neutralizing antibodies. Despite their broad reactivity, varian t viruses, resistant to neutralization, can be selected in vitro in th e presence of such antisera. We have previously shown that neutralizat ion resistance of an escape mutant with an amino acid substitution in the transmembrane protein (A582T) occurs because of alteration or a co nformational epitope that is recognized by neutralizing antibodies dir ected against the CD4 binding site. In this report we demonstrate that immune escape via a single-amino-acid substitution (A281V) within a c onserved region of the envelope glycoprotein gp120 confers neutralizat ion resistance against a broadly reactive neutralizing antiserum from a seropositive individual. We show this alteration affects V3 and addi tional regions unrelated to V3 or the CD4 binding site. Together with previous studies on escape mutants selected in vitro, our findings sug gest that immune-selective pressure can arise by multiple pathways.