Protein kinase A phosphorylation activates Vpr-induced cell cycle arrest during human immunodeficiency virus type 1 infection.

Abstract

Infection with human immunodeficiency virus type 1 (HIV-1) causes an inexorable depletion of CD4(+) T cells. The loss of these cells is particularly pronounced in the mucosal immune system during acute infection, and the data suggest that direct viral cytopathicity is a major factor. Cell cycle arrest caused by the HIV-1 accessory protein Vpr is strongly correlated with virus-induced cell death, and phosphorylation of Vpr serine 79 (S79) is required to activate G(2)/M cell cycle blockade. However, the kinase responsible for phosphorylating Vpr remains unknown. Our bioinformatic analyses revealed that S79 is part of a putative phosphorylation site recognized by protein kinase A (PKA). We show here that PKA interacts with Vpr and directly phosphorylates S79. Inhibition of PKA activity during HIV-1 infection abrogates Vpr cell cycle arrest. These findings provide new insight into the signaling event that activates Vpr cell cycle arrest, ultimately leading to the death of infected T cells.

• Authors: R Anthony Barnitz, Fengyi Wan, Vinay Tripuraneni, Diane L Bolton, Michael J Lenardo
• Journal: Journal of virology (J Virol) Vol. 84 Issue 13 Pg. 6410-24 (Jul 2010) ISSN: 1098-5514 [Electronic] United States
• PMID: 20392842 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• vpr Gene Products, Human Immunodeficiency Virus
• vpr protein, Human immunodeficiency virus 1
• Serine
• Cyclic AMP-Dependent Protein Kinases

Topics

• Cell Cycle
• Cell Line
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• HIV-1 (pathogenicity)
• Humans
• Lymphocytes (virology)
• Phosphorylation
• Serine (metabolism)
• vpr Gene Products, Human Immunodeficiency Virus (metabolism)