ALTERATION OF V3 LOOP CONTEXT WITHIN THE ENVELOPE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENHANCES NEUTRALIZATION

Neutralization of a chimeric human immunodeficiency virus (HIV) type 1 , containing the V3 loop of the MN isolate substituted within the HXB2 envelope, was enhanced up to 20-fold compared with the HXB2 or MN par ental isolates by human HIV-positive sera. MN V3 loop-specific monoclo nal antibodies were better able to recognize the chimeric virus compar ed with MN, staining a greater percentage of infected cells and exhibi ting slight increases in relative affinity with a concomitant increase in neutralization titer. Competition analysis revealed that enhanced neutralization by human HIV-positive sera of the chimera was attributa ble in some cases to better reactivity with the linear V3 loop epitope but in others to conformational loop epitopes or previously cryptic o r poorly recognized epitopes outside the loop region. Mice primed with a vaccinia virus-chimeric envelope recombinant and boosted with gp160 developed a spectrum of antibodies different from that of mice simila rly immunized with HXB2 or MN recombinants or that of naturally infect ed humans. The chimeric envelope elicited antibodies with enhanced bin ding to the native MN V3 loop; however, the sites seen by the BALB/c m ice were not neutralizing epitopes. Nevertheless, similar to the obser vations made with use of human sera, the chimeric virus was more readi ly neutralized by all of the immune mouse sera, an effect apparently m ediated by non-V3 loop epitopes. These studies illustrate that not onl y the V3 loop sequence and conformation but also its context within th e viral envelope influence neutralization.