2 NEUTRALIZING ANTI-V3 MONOCLONAL-ANTIBODIES ACT BY AFFECTING DIFFERENT FUNCTIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Monoclonal antibody (MAb) ICR41.1i (rat IgG2a) is specific for a confo rmation-dependent epitope of human immunodeficiency virus type 1 (HIV- 1) V3, and MAb F58 (mouse IgG1) recognizes the peptide IXXGPGR, at the tip of the V3 loop. Both MAbs neutralized HIV-1 strain IIIB in C8166 and HeLa-T4(CD4) cells. Neutralization by either MAb did not inhibit a ttachment of virus to target cells as determined by FAGS analysis, ELI SA or immunofluorescence, and such attachment was absolutely dependent on the availability of CD4 molecules. F58 inhibited virus-induced cel l-cell fusion, and reduced internalization of virions in direct propor tion to neutralization, In contrast, ICR41.1i had no effect on HIV-1-m ediated cell fusion or on internalization of virus. It was concluded t hat MAb F58 neutralized infectivity by inhibiting fusion of the virus with the cell and internalization of the viral core, and that ICR41.1i neutralized by inhibiting a post-fusion-internalization event. The po ssible mechanism by which a neutralizing antibody binds to the V3 loop and affects the function(s) of structures inside the virion is discus sed. Lastly, postattachment neutralization (PAN) was investigated. F58 mediated PAN at 21 degrees C and 35 degrees C. However, ICR41.1i gave PAN at 21 degrees C but not at 35 degrees C, suggesting that a temper ature-dependent event affecting the V3 loop had abrogated neutralizati on. Overall, it appears that antibodies to different epitopes within t he V3 loop neutralize by affecting very different functions of the vir us.