Activation of protein phosphatase-2A1 by HIV-1 Vpr Cell death causing peptide in intact CD4+ T cells and in vitro

• Published in: Journal of cellular biochemistry Vol. 94; no. 4; pp. 816 - 825
• Main Authors: Janoo, Anwar, Morrow, Peter W., Tung, H.Y. Lim
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2005
• Subjects: cell death; HIV-1; metabolic disturbances; protein phosphatase-2A; Vpr
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.20347

HIV‐1, the etiologic agent of human AIDS, causes cell death in host and non‐host cells via HIV‐1 Vpr, one of its auxiliary gene product. HIV‐1 Vpr can also cause cell cycle arrest in several cell types. The cellular processes that link HIV‐1 Vpr to the cell death machinery are not well characterized. Here, we show that the C terminal portion of HIV‐1 Vpr which encompasses amino acid residues 71–96 (HIV‐1 Vpr71–96), also termed HIV‐1 Vpr cell death causing peptide, is an activator of protein phosphatase‐2A1 when applied extracellularly to CD4+ T cells. HIV‐1 Vpr71–96 is a direct activator of protein phosphatase‐2A1 that has been purified from CD4+ T cells. Full length HIV‐1 Vpr by itself does not cause the activation of protein phosphatase‐2A1 in vitro. HIV‐1 Vpr71–96 also causes the activation of protein phosphatase‐2A0 and protein phosphatase‐2A1 from brain, liver, and adipose tissues. These results indicate that HIV‐1 can cause cell death of infected cells and non‐infected host and non‐host cells via HIV‐1 Vpr derived C terminal peptide(s) which act(s) by cell penetration and targeting of a key controller of the cell death machinery, namely, protein phosphatase‐2A1. The activation of other members of the protein phosphatase‐2A subfamily of enzymes which are involved in the control of several metabolic pathways in brain, liver, and adipose tissues by HIV‐1 Vpr derived C terminal peptide(s) may underlie various metabolic disturbances that are associated with HIV‐1 infection. © 2004 Wiley‐Liss, Inc.