Increased neutralization sensitivity and reduced replicative capacity of human immunodeficiency virus type 1 after short-term in vivo or in vitro passage through chimpanzees

Development of disease is extremely rare in chimpanzees when inoculated wit h either T-cell-line-adapted neutralization-sensitive or primary human immu nodeficiency virus type 1 (HIV-1), at first excluding a role for HIV-1 neut ralization sensitivity in the clinical course of infection. Interestingly, we observed that short-term in vivo and in vitro passage of primary HIV-1 i solates through chimpanzee peripheral blood mononuclear cells (PBMC) result ed in a neutralization-sensitive phenotype. Furthermore, an HIV-1 variant r eisolated from a chimpanzee 10 years after experimental infection was still sensitive to neutralization by soluble CD4, the CD4 binding site recognizi ng antibody IgG1b12 and autologous chimpanzee serum samples, but had become relatively resistant to neutralization by polyclonal human sera and neutra lizing monoclonal antibodies. The initial adaptation of HIV-1 to replicate in chimpanzee PBMC seemed to coincide with a selection for viruses with low replicative kinetics. Neither coreceptor usage nor the expression Level of CD4, CCR5, or CXCR4 on chimpanzee PBMC compared to human cells could expla in the phenotypic changes observed in these chimpanzee-passaged viruses. Ou r data suggest that the increased neutralization sensitivity of HIV-1 after replication in chimpanzee cells may in part contribute to the long-term as ymptomatic HIV-1 infection in experimentally infected chimpanzees.