GENOMIC AND BIOLOGICAL ALTERATION OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-SIMIAN IMMUNODEFICIENCY VIRUS-STRAIN MAC CHIMERA, WITH HIV-1 ENV, RECOVERED FROM A LONG-TERM CARRIER MONKEY

A macaque monkey infected with NM-3, a human immunodeficiency virus ty pe 1 (HIV-1)-simian immunodeficiency virus strain mac (SIVmac) chimeri c virus with env, rev, tat and vpu derived from HIV-1 and LTR, gag, po l, vif and vpx derived from SIVmac, became a long-term carrier (more t han 2 . 8 years), This monkey produced neutralizing antibodies to the original NM-3 as well as to the parental HIV-1, The virus recovered at 116 weeks replicated more rapidly and productively in macaque periphe ral blood mononuclear cells than the original virus, The recovered vir us was not neutralized either by antibodies raised early in the monkey or by a neutralizing monoclonal antibody that recognizes the V3 loop of HIV-1 Env, whereas both the early antibodies and the monoclonal ant ibody neutralized the original NM-3, Analysis of the virus genomic pop ulation revealed a few common mutations in the V3 region that caused a mino acid changes, These data are consistent with the hypothesis that the virus escaped from the early antibodies and that the observed muta tions contributed to this, as with HIV-1-infected humans, The observed mutations could equally well be the result of adaptation to simian ce lls, These results suggest that the HIV-1-SIVmac chimeric virus will b e useful for investigating genetic variation of HIV-1 env and alterati on of biological properties in vivo in relation to the frost immune re sponse.