Human immunodeficiency virus (HIV)-resistant CD4+ UT-7 megakaryocytic human cell line becomes highly HIV-1 and HIV-2 susceptible upon CXCR4 transfection: induction of cell differentiation by HIV-1 infection.
Recent findings have shown that the expression of the seven trans-membrane G-protein-coupled CXCR4 (the receptor for the stromal cell-derived factor [SDF]-1 chemokine) is necessary for the entry of T-lymphotropic human immunodeficiency virus (HIV) strains, acting as a coreceptor of the CD4 molecule. In the human system, the role of CXCR4 in HIV infection has been determined through env-mediated cell fusion assays and confirmed by blocking viral entry in CD4+/CXCR4+ cells by SDF-1 pretreatment. We observed that the human megakaryoblastic CD4+ UT-7 cell line fails to express CXCR4 RNA and is fully resistant to HIV entry. Transfection of an expression vector containing the CXCR4 c-DNA rendered UT-7 cells readily infectable by different T-lymphotropic syncytium-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 megakaryocytic differentiation and maturation. On the contrary, no morphologic changes were observed in HIV-2-infected UT-7/fus cells. These findings further strengthen the role of CXCR4 as a molecule necessary for the 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 infection.
Baiocchi
M
M
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Olivetta
E
E
Chelucci
C
C
Santarcangelo
A C
AC
Bona
R
R
d'Aloja
P
P
Testa
U
U
Komatsu
N
N
Verani
P
P
Federico
M
M
D015704:CD4 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000473:pathology; D008533:Megakaryocytes / Q000378:metabolism / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins