Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage

Coreceptor usage of primary human immunodeficiency virus type 1 (HIV-1) iso lates varies according to biological phenotype. The chemokine receptors CCR 5 and CXCR4 are the major coreceptors that, together with CD4, govern HIV-1 entry into cells. Since CXCR4 usage determines the biological phenotype fo r HIV-1 isolates and is more frequent in patients with immunodeficiency, it may serve as a marker for viral virulence. This possibility prompted us to study coreceptor usage by HIV-2, known to be less pathogenic than HIV-1. W e tested 11 primary HIV-2 isolates for coreceptor usage in human cell lines : U87 glioma cells, stably expressing CD4 and the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, and GHOST(3) osteosarcoma cells, coexpressing CD4 and CCR5, CXCR4, or the orphan receptor Bonzo or BOB. The indicator cel ls were infected by cocultivation with virus-producing peripheral blood mon onuclear cells and by cell-free virus. Our results show that 10 of 11 HIV-2 isolates were able to efficiently use CCR5. In contrast, only two isolates , both from patients with advanced disease, used CXCR4 efficiently. These t wo isolates also promptly induced syncytia in MT-2 cells, a pattern describ ed for HIV-1 isolates that use CXCR4. Unlike HIV-1, many of the HIV-2 isola tes were promiscuous in their coreceptor usage in that they were able to us e, apart from CCR5, one or more of the CCR1, CCR2b, CCR3, and BOB corecepto rs. Another difference between HIV-1 and HIV-2 was that the ability to repl icate in MT-2 cells appeared to be a general property of HIV-2 isolates. Ba sed on BOB mRNA expression in MT-2 cells and the ability of our panel of HI V-2 isolates to use BOB, we suggest that HIV-2 can use BOB when entering MT -2 cells. The results indicate no obvious link between viral virulence and the ability to use a multitude of coreceptors.