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Journal of Virology, January 1999, p. 92-100, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Vpu Increases Susceptibility of Human
Immunodeficiency Virus Type 1-Infected Cells to Fas Killing
Carolyn R.
Casella,1
Eric L.
Rapaport,1 and
Terri H.
Finkel1,2,*
Division of Basic Sciences, Department of
Pediatrics, National Jewish Medical and Research Center, Denver,
Colorado 80206,1 and
Departments of
Immunology, Pediatrics, and Biochemistry & Molecular Genetics,
University of Colorado Health Sciences Center, Denver, Colorado
802622
Received 2 July 1998/Accepted 25 September 1998
The importance of the Fas death pathway in human immunodeficiency
virus (HIV) infection has been the subject of many studies. Missing
from these studies is direct measurement of infected cell susceptibility to Fas-induced death. To address this question, we
investigated whether T cells infected with HIV are more susceptible to
Fas-induced death. We found that Fas cross-linking caused a decrease in
the number of HIV-infected Jurkat T cells and CD4+
peripheral blood leukocytes (PBLs). We confirmed this finding by
demonstrating that there were more apoptotic infected than uninfected
cells after Fas ligation. The increase in sensitivity of
HIV-infected cells to Fas killing mapped to vpu, while
nef, vif, vpr, and second exon of
tat did not appear to contribute. Furthermore, expression
of Vpu in Jurkat T cells rendered them more susceptible to Fas-induced
death. These results show that HIV-infected cells are more sensitive to
Fas-induced death and that the Vpu protein of HIV contributes to this
sensitivity. The increased sensitivity of HIV-infected cells to
Fas-induced death might help explain why these cells have such a short
in vivo half-life.
*
Corresponding author. Mailing address: National Jewish
Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1408. Fax: (303) 398-1225. E-mail:
finkelt{at}njc.org.
Journal of Virology, January 1999, p. 92-100, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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