Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal


Autoři: Wim Trypsteen aff001;  Cory H. White aff002;  Amey Mukim aff003;  Celsa A. Spina aff003;  Ward De Spiegelaere aff005;  Steve Lefever aff006;  Vicente Planelles aff007;  Alberto Bosque aff008;  Christopher H. Woelk aff002;  Linos Vandekerckhove aff001;  Nadejda Beliakova-Bethell aff003
Působiště autorů: HIV Cure Research Center, Department of Internal Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium aff001;  Faculty of Medicine, University of Southampton, Southampton, Hants, United Kingdom aff002;  San Diego VA Medical Center and Veterans Medical Research Foundation, San Diego, CA, United States of America aff003;  Department of Pathology, University of California San Diego, La Jolla, CA, United States of America aff004;  Department of Morphology, Faculty of Veterinary Sciences, Ghent University, Ghent, Belgium aff005;  Center for Medical Genetics, Ghent University, Ghent, Belgium aff006;  Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, United States of America aff007;  Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, United States of America aff008;  Department of Medicine, University of California San Diego, La Jolla, CA, United States of America aff009
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224879

Souhrn

The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models, we identified lncRNAs dysregulated in latency. PVT1 and RP11-347C18.3 were up-regulated in common between the two models, and RP11-539L10.2 was down-regulated. The major component of the latent HIV reservoir, memory CD4+ T-cells, had higher expression of these lncRNAs, compared to naïve T-cells. Guilt-by-association analysis demonstrated that lncRNAs dysregulated in latency were associated with several cellular pathways implicated in HIV latency establishment and maintenance: proteasome, spliceosome, p53 signaling, and mammalian target of rapamycin (MTOR). PVT1, RP11-347C18.3, and RP11-539L10.2 were down-regulated by latency reversing agents, suberoylanilide hydroxamic acid and Romidepsin, suggesting that modulation of lncRNAs is a possible secondary mechanism of action of these compounds. These results will facilitate prioritization of lncRNAs for evaluation as targets for HIV latency reversal. Importantly, our study provides insights into regulatory function of lncRNA during latent HIV infection.

Klíčová slova:

Gene expression – HIV infections – Long non-coding RNAs – Proteasomes – T cells – Viral persistence and latency – Spliceosomes


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