The DOI matches its Crossref record; 92 of the 95 references it cites were found in a registry or an index.
Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA
Open accessAbstract
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. Background: Exosomes are extracellular vesicles that have been implicated in intercellular communication. Results: Exosomes that originate from human cells infected with HIV-1 contain virus-derived small noncoding RNA. Conclusion: Virus-derived small RNA present in exosomes exert functional consequences in naive recipient cells. Significance: Viral RNA molecules present in exosomes may be critical mediators of intercellular viral spread in infected hosts.
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“It was reported that exosomes secreted by HIV-1-infected cells contained a trans-activation response element (TAR), an RNA structure involved in the activation of the viral 5′-LTR promoter, as well as cellular RNase III enzymes, Dicer and Drosha. Incubation with such exosomes increased the permissiveness of recipient cells to HIV-1 infection, and inhibited the apoptosis of infected cells [126].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [126]
Citations
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3 of the 95 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Carpio, 2010, microRNA machinery is an integral component of drug-induced transcription inhibition in HIV-1 infection, J. RNAi Gene Silencing, 6, 386
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Biological properties of extracellular vesicles and their physiological functions
Yáñez‐Mó, M., Siljander, P. R. ‐., Andreu, Z., Bedina Zavec, A., Borràs, F. E., Buzas, E. I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.27066 · Cited by 5,926
Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis
Melo, S. A., Sugimoto, H., O’Connell, J. T., Kato, N., Villanueva, A., Vidal, A., Qiu, L., Vitkin, E. I., Perelman, L. T., Melo, C. A., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.005 · Cited by 1,566
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Schorey, J. S., Cheng, Y., Singh, P., & Smith, V. L. (2014) · EMBO Reports · doi:10.15252/embr.201439363 · Cited by 752
Toro, J. D., Herschlik, L., Waldner, C., & Mongini, C. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00203 · Cited by 632
Extracellular vesicles and viruses: Are they close relatives?
Hoen, E. N. M. N., Cremer, T., Gallo, R. C., & Margolis, L. B. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1605146113 · Cited by 497
Metadata
- Authors
- Narayanan, A., Iordanskiy, S., Das, R., Van Duyne, R., Santos, S., Jaworski, E., Guendel, I., Sampey, G., Dalby, E., Iglesias-Ussel, M., Popratiloff, A., Hakami, R., Kehn-Hall, K., Young, M., Subra, C., Gilbert, C., Bailey, C., Romerio, F., & Kashanchi, F.
- Affiliations
- George Mason University (US)
- George Washington University (US)
- University of Maryland, Baltimore (US)
- Georgetown University Medical Center (US)
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Kashanchi, Fatah
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 288
- Issue
- 27
- Pages
- 20014-20033
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3707700
- OpenAlex
- W1991259997
- Cited by
- 316
- References
- 95
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 29 · 2023: 20 · 2022: 18 · 2021: 39 · 2020: 34 · 2019: 31 · 2018: 27 · 2017: 26 · 2016: 26 · 2015: 21 · 2014: 17 · 2013: 4
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P30AI087714, UO1-AI35004, UO1AI34993, R21AI078859, AI 078859, UO1-AI31834, AI074410, U01AI034989, U01AI031834, U01AI042590, R01AI043894, UO1-AI-34989, U01AI034993, U01AI034994, AI043894, R21AI074410, U01AI035004, UO1-AI-34994, UO1-AI-42590)
- National Center for Research Resources (UL1RR024131)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632, U01HD032632)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- exosomes, HIV-1, TAR RNA, viral microRNAs, extracellular vesicles, CRM1, Dicer, Drosha, Argonaute 2, apoptosis, building information modeling, CDK9, HIV-1 infection susceptibility, long-term nonprogressors, antiretroviral therapy, serum exosomes
- MeSH terms
- Bcl-2-Like Protein 11, Acquired Immunodeficiency Syndrome, HeLa Cells, Humans, Membrane Proteins, Proto-Oncogene Proteins, RNA, Viral, HIV-1, Down-Regulation, HIV Long Terminal Repeat, Cyclin-Dependent Kinase 9, Apoptosis Regulatory Proteins, Exosomes
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