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 virus type 1 (HIV-1). We have isolated a homolog of hCXCR-4 from a murine 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 concentrated in extracellular domains. Surprisingly, coexpression of both hCD4 and mCXCR-4 on either simian or murine cell lines rendered them permissive for HIV-1-induced cell fusion, indicating that mCXCR-4 is a functional HIV-1 coreceptor. As with hCXCR-4, coreceptor function was restricted to T-tropic and dual-tropic HIV-1 strains. Ribonuclease protection analysis indicated that mCXCR-4 mRNA was expressed in only two of six murine cell lines tested. In contrast, Northern blot analysis of human 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.
Bieniasz
P D
PD
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Fridell
R A
RA
Anthony
K
K
Cullen
B R
BR
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*
D008565:Membrane Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D015728:Receptors, HIV