Direct and indirect effects of CYTOR lncRNA regulate HIV gene expression
The implementation of antiretroviral therapy (ART) has effectively restricted the transmission of Human Immunodeficiency Virus (HIV) and improved overall clinical outcomes. However, a complete cure for HIV remains out of reach, as the virus persists in a stable pool of infected cell reservoir that i...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 25, 2024
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| In: |
PLoS pathogens
Year: 2024, Jahrgang: 20, Heft: 4, Pages: 1-22 |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1012172 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1371/journal.ppat.1012172 Verlag, kostenfrei, Volltext: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012172 
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| Verfasserangaben: | Alona Kuzmina, Lopamudra Sadhu, Md Hasanuzzaman, Koh Fujinaga, Jacob C. Schwartz, Oliver T. Fackler, Ran Taube |
| Zusammenfassung: | The implementation of antiretroviral therapy (ART) has effectively restricted the transmission of Human Immunodeficiency Virus (HIV) and improved overall clinical outcomes. However, a complete cure for HIV remains out of reach, as the virus persists in a stable pool of infected cell reservoir that is resistant to therapy and thus a main barrier towards complete elimination of viral infection. While the mechanisms by which host proteins govern viral gene expression and latency are well-studied, the emerging regulatory functions of non-coding RNAs (ncRNA) in the context of T cell activation, HIV gene expression and viral latency have not yet been thoroughly explored. Here, we report the identification of the Cytoskeleton Regulator (CYTOR) long non-coding RNA (lncRNA) as an activator of HIV gene expression that is upregulated following T cell stimulation. Functional studies show that CYTOR suppresses viral latency by directly binding to the HIV promoter and associating with the cellular positive transcription elongation factor (P-TEFb) to activate viral gene expression. CYTOR also plays a global role in regulating cellular gene expression, including those involved in controlling actin dynamics. Depletion of CYTOR expression reduces cytoplasmic actin polymerization in response to T cell activation. In addition, treating HIV-infected cells with pharmacological inhibitors of actin polymerization reduces HIV gene expression. We conclude that both direct and indirect effects of CYTOR regulate HIV gene expression. |
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| Beschreibung: | Gesehen am 25.10.2024 |
| Beschreibung: | Online Resource |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1012172 |