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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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