Journal article
Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA
The Journal of biological chemistry, v 291(3), pp 1251-1266
15 Jan 2016
PMID: 26553869
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HIV-1 infection results in a chronic illness because longterm highly active antiretroviral therapy can lower viral titers to an undetectable level. However, discontinuation of therapy rapidly increases virus burden. Moreover, patients under highly active antiretroviral therapy frequently develop various metabolic disorders, neurocognitive abnormalities, and cardiovascular diseases. We have previously shown that exosomes containing trans-activating response (TAR) element RNA enhance susceptibility of undifferentiated naive cells to HIV-1 infection. This study indicates that exosomes from HIV-1-infected primary cells are highly abundant with TAR RNA as detected by RT-real time PCR. Interestingly, up to a million copies of TAR RNA/ mu l were also detected in the serum from HIV-1-infected humanized mice suggesting that TAR RNA may be stable in vivo. Incubation of exosomes from HIV-1-infected cells with primary macrophages resulted in a dramatic increase of proinflammatory cytokines, IL-6 and TNF-beta, indicating that exosomes containing TAR RNA could play a direct role in control of cytokine gene expression. The intact TAR molecule was able to bind to PKR and TLR3 effectively, whereas the 5' and 3' stems (TAR microRNAs) bound best to TLR7 and -8 and none to PKR. Binding of TAR to PKR did not result in its phosphorylation, and therefore, TAR may be a dominant negative decoy molecule in cells. The TLR binding through either TAR RNA or TAR microRNA potentially can activate the NF-kB pathway and regulate cytokine expression. Collectively, these results imply that exosomes containing TAR RNA could directly affect the proinflammatory cytokine gene expression and may explain a possible mechanism of inflammation observed in HIV-1-infected patients under cART.
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Details
- Title
- Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA
- Creators
- Gavin C. Sampey - George Mason UniversityMohammed Saifuddin - George Mason UniversityAngela Schwab - George Mason UniversityRobert Barclay - George Mason UniversityShreya Punya - George Mason UniversityMyung-Chul Chung - George Mason UniversityRamin M. Hakami - George Mason UniversityMohammad Asad Zadeh - George Mason UniversityBenjamin Lepene - Ceres NanosciencesZachary A. Klase - University of the SciencesNazira El-Hage - College Station Medical CenterMary Young - Georgetown UniversitySergey Iordanskiy - George Mason UniversityFatah Kashanchi - George Mason University
- Publication Details
- The Journal of biological chemistry, v 291(3), pp 1251-1266
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 16
- Grant note
- F31NS086453 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) U01-AI-34994 / National Institutes of Health from NIAID; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) U01AI034994 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000368068300021
- Scopus ID
- 2-s2.0-84954540868
- Other Identifier
- 991021902600504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology