VARYING TEMPERATURE-DEPENDENCE OF POST ATTACHMENT NEUTRALIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BY MONOCLONAL-ANTIBODIES TO GP120 -IDENTIFICATION OF A VERY EARLY FUSION-INDEPENDENT EVENT AS A NEUTRALIZATION TARGET

Neutralization of human immunodeficiency virus type 1 by adding antibo dy after the virus has attached to the host cell (post-attachment neut ralization:PAN) was investigated using three rat monoclonal antibodies (MAbs) directed against the outer domain of the membrane protein, gp1 20, Two of the MAbs are specific for the CD4-binding site region and o ne for the V3 loop, MAb ICR39.13g (CD4-binding site region-specific; I gGZb) effected PAN efficiently at temperatures from 4 to 35 degrees C. MAb lCR41.1i (V3 loop-specific; IgG2c) effected PAN only at temperatu res of 24 degrees C and below. This suggests that its V3 epitope is ma sked by a change in gp120 which occurs at temperatures greater than or equal to 26 degrees C, or that the virion function which is inhibited by ICR41.1i and is responsible for neutralization has already operate d at greater than or equal to 26 degrees C. Resistance to neutralizati on by ICR41.1i occurred within 20 min of shifting the temperature up t o 35 degrees C. Finally, MAb ICR39.3b (CD4-binding site region-specifi c; IgG2b) did not give PAN at any temperature, indicating that neutral ization can only occur if this MAb binds virus before it attaches to t he cell, Thus, these studies identify at least one novel fusion-indepe ndent event, the neutralization target of a V3 MAb, which occurs very early in the initial stages of virus-cell interaction.