Journal article
Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA
The Journal of biological chemistry, v 288(27), pp 20014-20033
05 Jul 2013
PMID: 23661700
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Exosomes are nano-sized vesicles produced by healthy and virus-infected cells. Exosomes derived from infected cells have been shown to contain viral microRNAs (miRNAs). HIV-1 encodes its own miRNAs that regulate viral and host gene expression. The most abundant HIV-1-derived miRNA, first reported by us and later by others using deep sequencing, is the trans-activation response element (TAR) miRNA. In this study, we demonstrate the presence of TAR RNA in exosomes from cell culture supernatants of HIV-1-infected cells and patient sera. TAR miRNA was not in Ago2 complexes outside the exosomes but enclosed within the exosomes. We detected the host miRNA machinery proteins Dicer and Drosha in exosomes from infected cells. We report that transport of TAR RNA from the nucleus into exosomes is a CRM1 (chromosome region maintenance 1)-dependent active process. Prior exposure of naive cells to exosomes from infected cells increased susceptibility of the recipient cells to HIV-1 infection. Exosomal TAR RNA down-regulated apoptosis by lowering Bim and Cdk9 proteins in recipient cells. We found 10(4)-10(6) copies/ml TAR RNA in exosomes derived from infected culture supernatants and 10(3) copies/ml TAR RNA in the serum exosomes of highly active antiretroviral therapy-treated patients or long term nonprogressors. Taken together, our experiments demonstrated that HIV-1-infected cells produced exosomes that are uniquely characterized by their proteomic and RNA profiles that may contribute to disease pathology in AIDS.
Metrics
Details
- Title
- Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA
- Creators
- Aarthi Narayanan - George Mason UniversitySergey Iordanskiy - George Mason UniversityRavi Das - George Mason UniversityRachel Van Duyne - George Mason UniversitySteven Santos - George Washington UniversityElizabeth Jaworski - George Mason UniversityIrene Guendel - George Mason UniversityGavin Sampey - George Mason UniversityElizabeth Dalby - George Mason UniversityMaria Iglesias-Ussel - College Station Medical CenterAnastas Popratiloff - George Washington UniversityRamin Hakami - George Mason UniversityKylene Kehn-Hall - George Mason UniversityMary Young - Georgetown UniversityCaroline Subra - College Station Medical CenterCaroline Gilbert - College Station Medical CenterCharles Bailey - George Mason UniversityFabio Romerio - College Station Medical CenterFatah Kashanchi - George Mason University
- Publication Details
- The Journal of biological chemistry, v 288(27), pp 20014-20033
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 20
- Grant note
- 5P30AI087714-02 / District of Columbia Developmental Center for AIDS Research Grant UL1RR024131 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R21AI078859 / 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) NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U01HD032632 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) NIDCD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD) DE-SC0001599 / United States Department of Energy; United States Department of Energy (DOE) R01NS099029 / 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) UL1 RR024131 / NCRR UCSF-CTSI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) AI078859; AI074410; AI043894 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000321515800065
- Scopus ID
- 2-s2.0-84880065053
- Other Identifier
- 991021903312904721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology