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Journal of Virology, November 2005, p. 13735-13746, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13735-13746.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Vpr Interacts with Antiapoptotic Mitochondrial Protein HAX-1

Venkat S. R. K. Yedavalli,1,{dagger} Hsiu-Ming Shih,2,{dagger} Yu-Ping Chiang,3 Chun-Yi Lu,3 Luan-Yin Chang,3 Mao-Yuan Chen,4 Che-Yen Chuang,4 Andrew I. Dayton,5 Kuan-Teh Jeang,1* and Li-Min Huang3*

Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, Maryland 20892-0460,1 Institute of Biomedical Sciences, Academia Sinica,2 Department of Pediatrics,3 Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 100,4 Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892-04605

Received 13 April 2005/ Accepted 7 August 2005

Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr.

* Corresponding author. Mailing address for K.-T. Jeang: Building 4, Room 306, 9000 Rockville Pike, NIH, Bethesda, MD 20892-0460. Phone: (301) 496-6680. Fax: (301) 480-3686. E-mail: kj7e{at}nih.gov. Mailing address for L.-M. Huang: National Taiwan University Hospital, Department of Pediatrics, Taipei, Taiwan 10016. Phone: 886-2-2397-0800. Fax: (886) 22-2393-4749. E-mail: lmhuang{at}ha.mc.ntu.edu.tw.

{dagger} V.S.R.K.Y. and H.-M.S. contributed equally to this study.

Journal of Virology, November 2005, p. 13735-13746, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13735-13746.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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