HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CORECEPTORS PARTICIPATE IN POSTENTRY STAGES IN THE VIRUS-REPLICATION CYCLE AND FUNCTION IN SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION

Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection, Simian immunodeficiency virus (S IV) productively infects human cells expressing CD? and the human alle le of the chemokine coreceptor CCR-5 as efficiently as it infects maca que cells expressing human CD4, suggesting that SIV can function with either a simian or a human coreceptor in conjunction with human CD4. I n the same macaque cells expressing human CD4, the replication of huma n immunodeficiency virus type 1 (HIV-1) is blocked at several stages o f infection; some isolates are restricted prior to reverse transcripti on, while others, including some macrophage-tropic and primary isolate s, are restricted at a step after reverse transcription but prior to m igration of the preintegration complex to the nucleus, Both blocks in HIV-1 replication can he relieved by either expression of the appropri ate human coreceptor (CCR-5 or CXCR-4) or expression of SIV gene produ cts in cis with the HIV-1 envelope as a chimera between SIV and HIV-I (SHIV), Thus, a virus with a SIV core and HIV-1 envelope can efficient ly infect macaque cells expressing human CD4: presumably by interactin g with the simian coreceptor, whereas a virus with an HIV-I core and a n HIV-1 envelope requires expression of the human allele of the corece ptor for productive infection of these cells, These studies suggest th at there are interactions among the coreceptor, the viral envelope, an d another viral gene product that govern postentry steps of virus repl ication. These data are consistent with the hypothesis that such inter actions may be required for translocation of the virus core to the nuc leus, Moreover, the differential abilities of SIV and HIV-1 to functio n in these processes with heterologous primate coreceptors may have im plications for cross-species transmission.