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Journal of Virology, July 2007, p. 6947-6956, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02798-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Protease Cleaves Procaspase 8 In Vivo{triangledown}

Zilin Nie,1 Gary D. Bren,1 Stacey R. Vlahakis,1 Alicia Algeciras Schimnich,1 Jason M. Brenchley,3 Sergey A. Trushin,1 Sarah Warren,1 David J. Schnepple,1 Colin M. Kovacs,4 Mona R. Loutfy,4 Daniel C. Douek,3 and Andrew D. Badley1,2*

Division of Infectious Diseases,1 Program in Translational Immunovirology and Biodefense, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,2 VRC, NIAID, NIH, Human Immunology Section, Bethesda, Maryland 20892,3 Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5B 1L64

Received 19 December 2006/ Accepted 11 April 2007

Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It remains unknown what signals cause infected cells to die. We demonstrate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1-infected patients, casp8p41 is detected only in CD4+ T cells, predominantly in the CD27+ memory subset, its presence increases with increasing viral load, and it colocalizes with both infected and apoptotic cells. These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells.

* Corresponding author. Mailing address: Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905. Phone: (507) 284-3747. Fax: (507) 284-3757. E-mail: badley.andrew{at}mayo.edu

{triangledown} Published ahead of print on 18 April 2007.

Journal of Virology, July 2007, p. 6947-6956, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02798-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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