| Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa. | |
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MedLine Citation:
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PMID: 20838227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression. METHODS: In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4/μL), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.0 microarrays at 0, 2, 4, 8, and 24 weeks after ART initiation. RESULTS: We identified 160 mRNA transcripts that were consistently down-regulated and 48 that were up-regulated after ART at each point over 24 weeks based on linear regression modeling (adjusted P < 0.05), Of these 208 transcripts, approximately half represent heretofore unrecognized ART-responsive genes and one-third have no known function. The down-regulated genes with known function encoded mediators of innate antiviral responses, including antiviral restriction factors, pattern recognition receptors, and interferon response proteins, and mediators of immune activation, cellular proliferation, and apoptosis. CONCLUSIONS: By using ART to block the viral stimulus, we identified transcripts involved in innate antiviral immunity, including antiviral restriction factors and pattern recognition receptors, that were not previously known to be induced by HIV infection. |
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Authors:
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David R Boulware; David B Meya; Tracy L Bergemann; Darlisha Williams; Irina A Vlasova-St Louis; Josh Rhein; Jack Staddon; Andrew Kambugu; Edward N Janoff; Paul R Bohjanen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of acquired immune deficiency syndromes (1999) Volume: 55 ISSN: 1944-7884 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-05 Completed Date: 2011-01-04 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: United States |
Other Details:
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Languages: eng Pagination: 428-38 Citation Subset: IM; X |
Affiliation:
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Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acquired Immunodeficiency Syndrome
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drug therapy*,
immunology* Adult Anti-Retroviral Agents / pharmacology*, therapeutic use Antiretroviral Therapy, Highly Active Down-Regulation / drug effects Female HIV-1* Humans Immunity, Innate / drug effects*, genetics Male Microarray Analysis Middle Aged Prospective Studies Uganda |
| Grant Support | |
ID/Acronym/Agency:
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K23 AI073192-02/AI/NIAID NIH HHS; K23AI073192/AI/NIAID NIH HHS; L30 AI066779-04/AI/NIAID NIH HHS; L30AI066779/AI/NIAID NIH HHS; R01HD059527/HD/NICHD NIH HHS; R03 AI078750-01A1/AI/NIAID NIH HHS; R03AI078750/AI/NIAID NIH HHS; T32AI055433/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Retroviral Agents |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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