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Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus

The success of long-term host–virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus’s skill in manipulating its host to persist undetected yet replicate efficiently when needed. By mastering such skills, herpesviruses persist silent...

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Autores principales: Bhaduri-McIntosh, Sumita, McIntosh, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148530/
https://www.ncbi.nlm.nih.gov/pubmed/34066537
http://dx.doi.org/10.3390/v13050846
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author Bhaduri-McIntosh, Sumita
McIntosh, Michael T.
author_facet Bhaduri-McIntosh, Sumita
McIntosh, Michael T.
author_sort Bhaduri-McIntosh, Sumita
collection PubMed
description The success of long-term host–virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus’s skill in manipulating its host to persist undetected yet replicate efficiently when needed. By mastering such skills, herpesviruses persist silently in their hosts, though perturbations in this host–virus equilibrium can result in disease. The heterochromatin machinery that tightly regulates endogenous retroviral elements and pericentromeric repeats also silences invading genomes of alpha-, beta-, and gammaherpesviruses. That said, how these viruses disrupt this constitutive heterochromatin machinery to replicate and spread, particularly in response to disparate lytic triggers, is unclear. Here, we review how the cancer-causing gammaherpesvirus Epstein–Barr virus (EBV) uses the inflammasome as a security system to alert itself of threats to its cellular home as well as to flip the virus-encoded lytic switch, allowing it to replicate and escape in response to a variety of lytic triggers. EBV provides the first example of an infectious agent able to actively exploit the inflammasome to spark its replication. Revealing an unexpected link between the inflammasome and the epigenome, this further brings insights into how the heterochromatin machinery uses differential strategies to maintain the integrity of the cellular genome whilst guarding against invading pathogens. These recent insights into EBV biology and host–viral epigenetic regulation ultimately point to the NLRP3 inflammasome as an attractive target to thwart herpesvirus reactivation.
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spelling pubmed-81485302021-05-26 Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus Bhaduri-McIntosh, Sumita McIntosh, Michael T. Viruses Review The success of long-term host–virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus’s skill in manipulating its host to persist undetected yet replicate efficiently when needed. By mastering such skills, herpesviruses persist silently in their hosts, though perturbations in this host–virus equilibrium can result in disease. The heterochromatin machinery that tightly regulates endogenous retroviral elements and pericentromeric repeats also silences invading genomes of alpha-, beta-, and gammaherpesviruses. That said, how these viruses disrupt this constitutive heterochromatin machinery to replicate and spread, particularly in response to disparate lytic triggers, is unclear. Here, we review how the cancer-causing gammaherpesvirus Epstein–Barr virus (EBV) uses the inflammasome as a security system to alert itself of threats to its cellular home as well as to flip the virus-encoded lytic switch, allowing it to replicate and escape in response to a variety of lytic triggers. EBV provides the first example of an infectious agent able to actively exploit the inflammasome to spark its replication. Revealing an unexpected link between the inflammasome and the epigenome, this further brings insights into how the heterochromatin machinery uses differential strategies to maintain the integrity of the cellular genome whilst guarding against invading pathogens. These recent insights into EBV biology and host–viral epigenetic regulation ultimately point to the NLRP3 inflammasome as an attractive target to thwart herpesvirus reactivation. MDPI 2021-05-06 /pmc/articles/PMC8148530/ /pubmed/34066537 http://dx.doi.org/10.3390/v13050846 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bhaduri-McIntosh, Sumita
McIntosh, Michael T.
Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus
title Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus
title_full Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus
title_fullStr Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus
title_full_unstemmed Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus
title_short Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus
title_sort inflammasome, the constitutive heterochromatin machinery, and replication of an oncogenic herpesvirus
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148530/
https://www.ncbi.nlm.nih.gov/pubmed/34066537
http://dx.doi.org/10.3390/v13050846
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