| HIV-1 trans-activator protein dysregulates IFN-γ signaling and contributes to the suppression of autophagy induction. | |
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MedLine Citation:
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PMID: 21099673 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE AND DESIGN: HIV-1 transactivator protein, Tat, has been identified as an activator of HIV-1 replication. It also dysregulates cytokine production and apoptosis in T-cells. Of the various cell death processes, autophagy is a self-digestion and degradation mechanism that recycles the contents of the cytosol, including macromolecules and cellular organelles, resulting in self-repair and conservation for survival. Recent reports demonstrated that autophagosomes can be activated by interferon-γ (IFN-γ) to participate in immune defence by processing foreign antigens for the recognition and killing of intracellular pathogens. As we previously showed that HIV-1 Tat perturbs IFN-γ signaling through the suppression of STAT1 phosphorylation and consequently inhibits major histocompatibility complex class-II antigen expression, we postulate that Tat plays a role in regulating autophagy. METHODS: The role of STAT1 in IFN-γ-induced autophagy in primary human blood macrophages was examined using a small molecule inhibitor or siRNA specific for STAT1. The effect of HIV-1 Tat on autophagy was investigated by pretreating the macrophages with HIV-1 Tat and followed by IFN-γ stimulation. The expressions of autophagy-associated genes and their effects on engulfing mycobacteria were examined. RESULTS: The activation of STAT1 resulted in IFN-γ-induced LC3B protein expression and autophagosome formation. As postulated, HIV-1 Tat protein suppressed IFN-γ-induced autophagy processes, including LC3B expression. Additionally, HIV-1 Tat restricted the capturing of mycobacteria by autophagosomes. CONCLUSION: HIV-1 Tat suppressed the induction of autophagy-associated genes and inhibited the formation of autophagosomes. Perturbation of such cellular processes by HIV-1 would impair the effective containment of invading pathogens, thereby providing a favorable environment for opportunistic microbes in HIV-infected individuals. |
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Authors:
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James C B Li; Kin-yi Au; Jun-wei Fang; Howard C H Yim; Kin-hung Chow; Pak-leung Ho; Allan S Y Lau |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: AIDS (London, England) Volume: 25 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-01 Completed Date: 2011-03-25 Revised Date: 2011-04-19 |
Medline Journal Info:
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Nlm Unique ID: 8710219 Medline TA: AIDS Country: England |
Other Details:
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Languages: eng Pagination: 15-25 Citation Subset: IM; X |
Affiliation:
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Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Autophagy*
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genetics,
immunology Blotting, Western Cells, Cultured HIV Infections / genetics, metabolism* HIV-1 / pathogenicity* Humans Interferon-gamma / metabolism* Macrophages / immunology Signal Transduction / genetics, immunology* Transcriptional Activation tat Gene Products, Human Immunodeficiency Virus / genetics, immunology*, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/tat Gene Products, Human Immunodeficiency Virus; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
Erratum In:
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AIDS. 2011 Jan 28;25(3):395-6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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