Inter-subtype cross-neutralizing antibodies recognize epitopes on cell-associated HIV-1 virions

HIV-1 infected individuals with cross-neutralizing antibodies against primary HIV-1 isolates belonging to Group M (envA-H) and O, are identified. To investigate the neutralization-kinetics of primary isolates with these antibodies, different neutralization assay conditions are compared. Each set is summarized as a/b/c where a is the time in hours for which antibody is incubated with virus, b is the time in hours allowed for virus to absorb to cells, c is the total culture period in days, from the cells' first exposure to virus, before antigen production (peripheral blood mononuclear cells) or number of fluorescent cells (GHOST) are measured. In HIV-infected individuals, neutralizing antibodies can be detected against a wide range of primary isolates (Group M; A-H and Group O) in PBMC-assays with short incubation phases (1/2/7 or 1/24/7). If cultures are extended (1/2/14 or 1/24/14), however, neutralization can be lost. In kinetic experiments, neutralization can even be seen without pre-incubation (a=0 hr). This study shows that neutralization of primary HIV isolates by cross-reactive antibodies can continue after the virus has bound to its target cell. This neutralization, however, is not an all or nothing loss in virus infectivity. Most often it leads only to a reduction in viral replication rates.