THE SIMIAN IMMUNODEFICIENCY VIRUS MND(GB-1) STRAIN USES CXCR4, NOT CCR5, AS CORECEPTOR FOR ENTRY IN HUMAN-CELLS

The simian immunodeficiency virus (SIV) mnd(GB-1) strain, isolated fro m a mandrill, replicates in a human T cell line, CEM cells, and is inh ibited by the CXC-chemokines, stromal cell-derived factor 1 alpha and 1 beta(SDF-1 alpha/SDF-1 beta), the natural ligands for CXCR4. The IC5 0 was around 70-80 ng/ml, which corresponds to the IC50 of SDF-1 alpha /SDF-1 beta for T-tropic human immunodeficiency virus type 1 (HIV-1) a nd HIV-2. The specific anti-CXCR4 MAb 12G5 inhibited replication of SI Vmnd at an IC50 of 1 mu g/ml. Also, the IC50 of 8 ng/ml for SIVmnd of the bicyclam AMD3100, a specific CXCR4 antagonist, is comparable with its IC50 for T-tropic HIV-1 and HIV-2 strains. Two other SIV strains, SIVagm3 and SIVmac251, were insensitive to SDF-1 alpha/SDF-1 beta, ant i-CXCR4 MAb and AMD3100. SIVmnd replicates only in HOS.CD4 cells expre ssing CXCR4 and not in HOS.CD4 transfectants expressing CCR1, CCR2b, C CR3, CCR4 or CCR5. This is, to our knowledge, the first SIV strain fou nd to use CXCR4 and not CCR5 as a main coreceptor for entering human c ells.