Receptor function of CD4 structures from African green monkey and pig-tail macaque for simian immunodeficiency virus, SIVsm, SIVagm, and human immunodeficiency virus type-1

Differences in kinetics of infection, cellular tropism, and cytopathology of SIV and HIV appear to depend on both viral and host factors. We investigated the role of critical CD4 structures from African green monkeys (AGM) a natural SIV host, from pig-tailed macaques (PT) an unnatural SIV host, and from humans, as well as the role of species-specific cellular factors involved in the tropism, kinetics of infection, and cytopathic effects of several SIV and HIV. Critical regions of the PT macaque and AGM CD4 genes (V1, V1J1, and V1J1V2J2) were stably expressed as chimeras with the human CD4 gene in human (HeLa and 293) and macaque (CMMT) cell lines. CD4 expressing cell lines were used for infection studies with cell-free SIVsm, SIVmac, SIVsmmPBj, SIVagm, and HIV-1. Results show that both PT CD4 and AGM CD4 supported infection with comparable infection kinetics by all SIV or HIV-1 strains tested. Although structural analysis predicted a major change in secondary structure of AGM CD4/CDR-3, these structural changes did not influence the degree of syncytia formation induced by several SIV and HIV-1. However, the cell line used to express the CD4 gene appeared to be a critical determinant of infection. Thus, SIV strains did not infect human cell lines regardless of the CD4 expressed in these cells. In contrast, HIV-1 did not infect any macaque cell line. This study demonstrates that the differences in CD4 structure among different primate species are clearly not responsible for differences in SIV and HIV infection kinetics, tropism, and cytopathology. However, species-specific factor(s), presumably expressed on the cell surface, markedly influences the ability of SIV or HIV to infect cells expressing CD4.