HIV Protease Cleavage of Procaspase 8 is Necessary for Death of HIV-Infected Cells



Zilin Nie1, §, Gary D Bren1, §, Stacey A Rizza1, 2, Andrew D Badley*, 1, 2
1 Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
2 Program in Translational Immunovirology and Biodefense, Mayo Clinic College of Medicine, Rochester, MN 55905, USA


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2008 Bentham Science Publishers Ltd.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/) which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Tel: 507-266-5065; Fax: 507-284-3757; E-mail: badley.andrew@mayo.edu
§ These authors contributed equally.


Abstract

Numerous host and viral factors are capable of causing death of HIV infected cells, uninfected bystander cells, or both. We assessed the relevance of HIV protease in infected cell killing by mutating its obligate substrate for death, procaspase 8. VSV pseudotyped HIV infection of cells expressing WT caspase 8 resulted in apoptotic cell death and generation of the HIV protease specific cleavage product of procaspase 8, casp8p41. Conversely, both cell death and casp8p41 production were inhibited in cells expressing procaspase 8 engineered to be resistant to HIV protease cleavage. Lymph nodes from HIV-infected patients with ongoing viral replication also selectively expressed casp8p41, which colocalized with both infected and apoptotic cells. HIV protease cleavage of procaspase 8 appears to be a necessary event for infected cell killing, which is responsible for infected cell death within lymphoid tissues from HIV-infected patients.