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Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy

The ability to establish, and reactivate from, latent infections is central to the biology and pathogenesis of HSV-1. It also poses a strong challenge to antiviral therapy, as latent HSV-1 genomes do not replicate or express any protein to be targeted. Although the processes regulating the establish...

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Autores principales: Schang, Luis M., Hu, MiYao, Cortes, Esteban Flores, Sun, Kairui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277756/
https://www.ncbi.nlm.nih.gov/pubmed/34082058
http://dx.doi.org/10.1016/j.antiviral.2021.105103
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author Schang, Luis M.
Hu, MiYao
Cortes, Esteban Flores
Sun, Kairui
author_facet Schang, Luis M.
Hu, MiYao
Cortes, Esteban Flores
Sun, Kairui
author_sort Schang, Luis M.
collection PubMed
description The ability to establish, and reactivate from, latent infections is central to the biology and pathogenesis of HSV-1. It also poses a strong challenge to antiviral therapy, as latent HSV-1 genomes do not replicate or express any protein to be targeted. Although the processes regulating the establishment and maintenance of, and reactivation from, latency are not fully elucidated, the current general consensus is that epigenetics play a major role. A unifying model postulates that whereas HSV-1 avoids or counteracts chromatin silencing in lytic infections, it becomes silenced during latency, silencing which is somewhat disrupted during reactivation. Many years of work by different groups using a variety of approaches have also shown that the lytic HSV-1 chromatin is distinct and has unique biophysical properties not shared with most cellular chromatin. Nonetheless, the lytic and latent viral chromatins are typically enriched in post translational modifications or histone variants characteristic of active or repressed transcription, respectively. Moreover, a variety of small molecule epigenetic modulators inhibit viral replication and reactivation from latency. Despite these successes in culture and animal models, it is not obvious how epigenetic modulation would be used in antiviral therapy if the same epigenetic mechanisms governed viral and cellular gene expression. Recent work has highlighted several important differences between the viral and cellular chromatins, which appear to be of consequence to their respective epigenetic regulations. In this review, we will discuss the distinctiveness of the viral chromatin, and explore whether it is regulated by mechanisms unique enough to be exploited in antiviral therapy.
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spelling pubmed-82777562021-08-01 Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy Schang, Luis M. Hu, MiYao Cortes, Esteban Flores Sun, Kairui Antiviral Res Article The ability to establish, and reactivate from, latent infections is central to the biology and pathogenesis of HSV-1. It also poses a strong challenge to antiviral therapy, as latent HSV-1 genomes do not replicate or express any protein to be targeted. Although the processes regulating the establishment and maintenance of, and reactivation from, latency are not fully elucidated, the current general consensus is that epigenetics play a major role. A unifying model postulates that whereas HSV-1 avoids or counteracts chromatin silencing in lytic infections, it becomes silenced during latency, silencing which is somewhat disrupted during reactivation. Many years of work by different groups using a variety of approaches have also shown that the lytic HSV-1 chromatin is distinct and has unique biophysical properties not shared with most cellular chromatin. Nonetheless, the lytic and latent viral chromatins are typically enriched in post translational modifications or histone variants characteristic of active or repressed transcription, respectively. Moreover, a variety of small molecule epigenetic modulators inhibit viral replication and reactivation from latency. Despite these successes in culture and animal models, it is not obvious how epigenetic modulation would be used in antiviral therapy if the same epigenetic mechanisms governed viral and cellular gene expression. Recent work has highlighted several important differences between the viral and cellular chromatins, which appear to be of consequence to their respective epigenetic regulations. In this review, we will discuss the distinctiveness of the viral chromatin, and explore whether it is regulated by mechanisms unique enough to be exploited in antiviral therapy. 2021-06-01 2021-08 /pmc/articles/PMC8277756/ /pubmed/34082058 http://dx.doi.org/10.1016/j.antiviral.2021.105103 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Schang, Luis M.
Hu, MiYao
Cortes, Esteban Flores
Sun, Kairui
Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy
title Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy
title_full Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy
title_fullStr Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy
title_full_unstemmed Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy
title_short Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy
title_sort chromatin-mediated epigenetic regulation of hsv-1 transcription as a potential target in antiviral therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277756/
https://www.ncbi.nlm.nih.gov/pubmed/34082058
http://dx.doi.org/10.1016/j.antiviral.2021.105103
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