SIMIAN IMMUNODEFICIENCY VIRUS VARIANTS WITH DIFFERENTIAL T-CELL AND MACROPHAGE TROPISM USE CCR5 AND AN UNIDENTIFIED COFACTOR EXPRESSED IN CEMX174 CELLS FOR EFFICIENT ENTRY

The recent identification of coreceptors that mediate efficient entry of human immunodeficiency virus type 1 (HIV-1) suggests new therapeuti c and preventive strategies. We analyzed simian immunodeficiency virus (SIV) entry cofactors to investigate whether the macaque SIV model ca n be used as an experimental model to evaluate these strategies. Simil ar to primary HIV-1 isolates, a well characterized molecular clone, SI Vmac239, which replicates poorly but efficiently enters into rhesus al veolar macrophages and an envelope variant, SIVmac239/316Env, with an similar to 1,000-fold-higher replicative capacity in macrophages used the beta-chemokine receptor CCR5 for efficient entry. The transmembran e portion of 316Env allowed low-level entry into cells expressing CCR1 , CCR2B, and CCR3. A single amino acid substitution in the V3 loop of SIVmac239/316Env, 321P-->S, impaired the ability to enter into the T-B hybrid cell line CEMx174 but had relatively little effect on entry in to primary cells and HOS.CD4 cells expressing CCR5. Although CEMx174 c ells do not express CCR5, most SIVmac variants entered this hybrid cel l line efficiently but did not enter the parental T-cell line CEM. It seems likely that CEMx174 cells express an as-yet-unidentified, perhap s B-cell-derived cofactor which allows efficient entry of SIVmac.