ArticleJournal of virology2019
Sirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Dynamic regulation of TBK1 lactylation shapes antiviral immune responses.Cellular & molecular immunology · 2026Article
- Epigenetic and epitranscriptomic regulation during oncogenicFrontiers in microbiology · 2024Review
- Immune evasion strategy involving propionylation by the KSHV interferon regulatory factor 1 (vIRF1).PLoS pathogens · 2023Article
- RNF213 modulates γ-herpesvirus infection and reactivation via targeting the viral Replication and Transcription Activator.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases.Frontiers in physiology · 2022Review
- Virus-Host Interplay Between Poly (ADP-Ribose) Polymerase 1 and Oncogenic Gammaherpesviruses.Frontiers in microbiology · 2021Review
- Quantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.Cell reports · 2020Article
- Regulation of KSHV Latency and Lytic Reactivation.Viruses · 2020Review
- Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV.PLoS pathogens · 2020Article
- Pathogenesis of Human Gammaherpesviruses: Recent Advances.Current clinical microbiology reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8 [HHV-8]), upon being reactivated, causes serious diseases in immunocompromised individuals. Its reactivation, especially how the cellular regulating mechanisms play roles in KSHV gene expression and viral DNA replication, is not fully understood. In searching for the cellular factors that regulate KSHV gene expression, we found that several histone deacetylases (HDACs) and sirtuins (SIRTs), including HDACs 2, 7, 8, and 11 and SIRTs 4 and 6, repress KSHV ori-Lyt promoter activity. Interestingly, the nuclear protein SIRT6 presents the greatest inhibitory effect on ori-Lyt promoter activity. A more detailed investigation revealed that SIRT6 exerts repressive effects on multiple promoters of KSHV. As a consequence of inhibiting the KSHV promoters, SIRT6 not only represses viral protein production but also inhibits viral DNA replication, as investigated in a KSHV-containing cell line, SLK-iBAC-gfpK52. Depletion of the SIRT6 protein using small interfering RNA could not directly reactivate KSHV from SLK-iBAC-gfpK52 cells but made the reactivation of KSHV by use of a small amount of the reactivator (doxycycline) more effective and enhanced viral DNA replication in the KSHV infection system. We performed DNA chromatin immunoprecipitation (ChIP) assays for SIRT6 in the SLK-iBAC-gfpK52 cell line to determine whether SIRT6 interacts with the KSHV genome in order to exhibit regulatory effects. Our results suggest that SIRT6 interacts with KSHV ori-Lyt and ORF50 promoters. Furthermore, the SIRT6-KSHV DNA interaction is significantly negated by reactivation. Therefore, we identified a cellular regulator, SIRT6, that represses KSHV replication by interacting with KSHV DNA and inhibiting viral gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.