HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)-RESISTANT CD4(-7 MEGAKARYOCYTIC HUMAN CELL-LINE BECOMES HIGHLY HIV-1 AND HIV-2 SUSCEPTIBLE UPON CXCR4 TRANSFECTION - INDUCTION OF CELL-DIFFERENTIATION BY HIV-1 INFECTION() UT)

Recent findings have shown that the expression of the seven trans-memb rane G-protein-coupled CXCR4 (the receptor for the stromal cell-derive d factor [SDF]-1 chemokine) is necessary for the entry of T-lymphotrop ic human immunodeficiency virus (HIV) strains, acting as a coreceptor of the CD4 molecule. In the human system, the role of CXCR4 in HIV inf ection has been determined through env-mediated cell fusion assays and confirmed by blocking viral entry in CD4(+)/CXCR4(+) cells by SDF-1 p retreatment. We observed that the human megakaryoblastic CD4(+) UT-7 c ell line fails to express CXCR4 RNA and is fully resistant to HIV entr y. Transfection of an expression vector containing the CXCR4 c-DNA ren dered UT-7 cells readily infectable by different T-lymphotropic syncyt ium-inducing HIV-1 and HIV-2 isolates. Interestingly, HIV-1 infection of CXCR4 expressing UT-7 cells (named UT-7/fus) induces the formation of polynucleated cells through a process highly reminiscent of megakar yocytic differentiation and maturation. On the contrary, no morphologi c changes were observed in HIV-2-infected UT-7/fus cells. These findin gs further strengthen the role of CXCR4 as a molecule necessary for th e replication of T-lymphotropic HIV-1 and HIV-2 isolates and provide a useful model to study the functional role of CD4 coreceptors in HIV i nfection. (C) 1997 by The American Society of Hematology.