Use of inhibitors to evaluate coreceptor usage by simian and simian/human immunodeficiency viruses and human immunodeficiency virus type 2 in primarycells

We have used coreceptor-targeted inhibitors to investigate which coreceptor s are used by human immunodeficiency virus type I (HIV-1), simian immunodef iciency viruses (SIV), and human immunodeficiency virus type 2 (HIV-2) to e nter peripheral blood mononuclear cells (PBMC). The inhibitors are TAK-779, which is specific for CCR5 and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5 and CCR3, and AMD3100, which targets CXCR4. We found that fo r ail the HIV-1 isolates and all hut one of the HIV-2 isolates tested, the only relevant coreceptors were CCR5 and CXCR4. However, one HIV-2 isolate r eplicated in human PBMC even in the presence of TAK-779 and AMD3100, sugges ting that it might use an undefined, alternative coreceptor that is express ed in the cells of some individuals. SIV(mac)239 and SIV(mac)251 (from maca ques) were also able to use an alternative coreceptor to enter PBMC from so me, but not all, human and macaque donors. The replication in human PBMC of SIVrcm (from a red-capped mangabey), a virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting that CCR2 is indeed the param ount coreceptor for this virus in primary cells.