SERIAL IN-VIVO PASSAGE OF HIV-1 INFECTION IN MACACA-NEMESTRINA

In an earlier study we found that pigtailed macaques (Macaca nemestrin a) that were experimentally infected with human immunodeficiency virus type 1 (HIV-I) initially became viremic and seroconverted, but HIV-1 replication diminished markedly over time. In an attempt to develop a longer term pathogenic model, blood from HIV-l-infected macaques was s erially transfused into three groups of naive macaques. Transfer was s uccessful through two transfusions as shown by repeated virus isolatio ns and confirmed by the development of cell-free plasma viremia and by seroconversion. Three to five weeks after transfusion, plasma levels of HIV-l RNA from several macaques in the first two groups exceeded th ose of the initially inoculated macaques. However, animals in the thir d group had diminished RNA levels, were virus culture negative, and di d not seroconvert Sequence analyses of env-region clones from infected animals revealed only minimal changes over the course of the passages . These results confirm HIV-I replication in M. nemestrina during the acute phase of infection. However, adaptation of HIV-1 to a macaque-pa thogenic variant did not occur during serial passage, possibly because the animals were able to restrict HIV-1 replication below a level req uired for a pathogenic variant to emerge. Whether such containment is a function of the host's immune response or a virus cell incompatibili ty remains to be determined. (C) 1997 Academic Press.