MURINE CXCR-4 IS A FUNCTIONAL CORECEPTOR FOR T-CELL-TROPIC AND DUAL-TROPIC STRAINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

The human chemokine receptor hCXCR-4 serves as a coreceptor for T-cell -tropic (T-tropic) and dual-tropic strains of human immunodeficiency v irus type I (HIV-1). We have isolated a homolog of hCXCR-4 from a muri ne T-cell cDNA library and have examined its ability to function as an HIV-1 coreceptor. mCXCR-4 was found to be 91% identical to the human receptor at the amino acid level, with sequence differences concentrat ed in extracellular domains. Surprisingly, coexpression of both hCD4 a nd mCXCR-4 on either simian or murine cell lines rendered them permiss ive for HIV-1-indnced cell fusion, indicating that mCXCR-4 is a functi onal HIV-1 coreceptor. As with hCXCR-4, coreceptor function was restri cted to T-tropic and dual-tropic HIV-I strains. Ribonuclease protectio n analysis indicated that mCXCR-4 mRNA was expressed in only two of si x murine cell lines tested. In contrast, Northern blot analysis of hum an and mouse tissues revealed that CXCR-4 is widely expressed in both species in vivo. Overall, these data suggest that the reported lack of susceptibility of hCD4(+) murine cells to HIV-1 infection in vitro is , at least in part, due to a lack of mCXCR-4 expression rather than a lack of coreceptor function.