A CXC chemokine receptor, CXCR5/BLR1, is a novel and specific coreceptor for human immunodeficiency virus type 2

G protein-coupled receptors serve as coreceptors in the infection process o f human immunodeficiency virus type-1 (HIV-1), type-2 (HIV-2), and simian i mmunodeficiency virus (SIV). In this study, we showed that a CXC-CKR, CXCR5 /BLR1, is a novel coreceptor for HIV-2, but for neither HIV-1 nor SIV. The expression of CXCR5 was detected by polymerase chain reaction after reverse transcription of cellular mRNA from S+L-HOS/CD4 cells and MT-2 human T cel ls, and the CXCR5 gene was cloned into an expression vector. S+L-HOS/CD4 ce lls were susceptible to several HIV-2 strains but not most HIV-1 strains. T o examine a coreceptor activity of CXCR5, we used NP-2/CD4, which is a huma n glioma cell line, NP-2, transduced with the CD4 gene that shows strict re sistance to infection with HIV-1, HIV-2, SIVmac, SIVagm, or SIVmnd strain. When CXCR5 was transduced into NP-2/CD4 cells, they became highly susceptib le to HIV-2ROD and HIV-2CBL23 strains in a CD4-dependent manner but to not to HIV-1 or SIV strains. Anti-CXCR5 monoclonal antibody and a ligand for CX CR5, BCA-1, inhibited HIV-2 infection to NP-2/CD4/CXCR5 cells. Our findings suggest a possibility that CXCR5/BLR1 serves as a coreceptor for HIV-2 str ains in vivo. (C) 1999 Academic Press.