Chen Z, Zhou P, Landau NR, Marx PA; Aaron Diamond AIDS Research Center, New York, NY.
Entry of HIV-1 requires CD4 and one of the seven-transmembrane domain coreceptors. M-tropic HIV-1 isolates are generally specific for CCR5 while T-tropic viruses tend to use CXCR4. Like HIV-1/2, SIV requires CD4 on the target cell surface; however, whether it also requires a coreceptor is not known. We report here that divergent strains of SIV, including SIVmac, SIVsm and SIVcpz, require CCR5 on the target cells which coexpress either human or rhesus CD4. None of the simian viruses tested were specific for other chemokine receptors, including CXCR4. Sequence analysis of rhesus CCR5 showed that the simian and human proteins differ at only 8 amino acid residues, including 4 in extracellular regions. The human coreceptor was found to be as active as the simian for SIV entry. In addition, HIV-1 was able to use the rhesus coreceptors, Rh-CCR5 and Rh-CXCR4 for entry. Unlike HIV-1, only Rh-CCR5 and Hu-CCR5 function as coreceptors for human T-cell line adapted or macrophage competent SIV strains. Unexpectedly, the replication of SIV was not restricted to cells expressing CCR5. SIV replicated robustly in the CEMx174 cell line which do not express detectable amounts of CCR5 as well as in human PBMC containing homozygous CCR5 defect. This finding suggests that SIV can use another, yet unidentified coreceptor. Finally, various SIV and HIV-1 can also use chimpanzee CCR5 as a coreceptor. The findings indicate that rhesus and chimpanzee CD4 and coreceptors do not appear to be the species restriction for HIV-1 infection.
Keywords: AEGIS, SIV, HIV-2, Antigens, CD4, HIV-1, Receptors, Chemokine, Virus Replication, Cell Line, Tumor Cells, Cultured, Macrophages, Human, virology, AIDS
