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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
M Baiocchi, E Olivetta, C Chelucci, AC Santarcangelo, R Bona, P d'Aloja, U Testa, N Komatsu, P Verani and M Federico
Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy.
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.
Volume 89,
Issue 8,
pp. 2670-2678,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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