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Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line.

Authors
  • Chugh, Pauline1
  • Fan, Shongshan
  • Planelles, Vicente
  • Maggirwar, Sanjay B
  • Dewhurst, Stephen
  • Kim, Baek
  • 1 Department of Microbiology and Immunology, School of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 672, Rochester, NY 14742, USA.
Type
Published Article
Journal
Journal of Molecular Biology
Publisher
Elsevier
Publication Date
Feb 09, 2007
Volume
366
Issue
1
Pages
67–81
Identifiers
PMID: 17157319
Source
Medline
Language
English
License
Unknown

Abstract

The interaction of human immunodeficiency virus type 1 (HIV-1) with CD4+ T lymphocytes is well studied and typically results in virally induced cytolysis. In contrast, relatively little is known concerning the interplay between HIV-1 and microglia. Recent findings suggest that, counter-intuitively, HIV-1 infection may extend the lifespan of microglia. We developed a novel cell line model system to confirm and mechanistically study this phenomenon. We found that transduction of a human microglial cell line with an HIV-1 vector results in a powerful cytoprotective effect following apoptotic challenge. This effect was reproduced by ectopic expression of a single virus-encoded protein, Tat. Subsequent studies showed that the pro-survival effects of intracellular Tat could be attributed to activation of the PI-3-kinase (PI3K)/Akt pathway in the microglial cell line. Furthermore, we found that expression of Tat led to decreased expression of PTEN, a negative regulator of the PI-3-K pathway. Consistent with this, decreased p53 activity and increased E2F activity were observed. Based on these findings, a model of possible regulatory circuits that intracellular Tat and HIV-1 infection engage during the cytoprotective event in microglia has been suggested. We propose that the expression of Tat may enable HIV-1 infected microglia to survive throughout the course of infection, leading to persistent HIV-1 production and infection in the central nervous system.

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