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An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles
Human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) persist as life-long infections alternating between latency and lytic replication. Human endogenous retroviruses (HERVs), via integration into the host genome, represent genetic remnants of ancient r...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381357/ https://www.ncbi.nlm.nih.gov/pubmed/34434177 http://dx.doi.org/10.3389/fmicb.2021.708404 |
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author | Frey, Tiffany R. Akinyemi, Ibukun A. Burton, Eric M. Bhaduri-McIntosh, Sumita McIntosh, Michael T. |
author_facet | Frey, Tiffany R. Akinyemi, Ibukun A. Burton, Eric M. Bhaduri-McIntosh, Sumita McIntosh, Michael T. |
author_sort | Frey, Tiffany R. |
collection | PubMed |
description | Human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) persist as life-long infections alternating between latency and lytic replication. Human endogenous retroviruses (HERVs), via integration into the host genome, represent genetic remnants of ancient retroviral infections. Both show similar epigenetic silencing while dormant, but can reactivate in response to cell signaling cues or triggers that, for gammaherpesviruses, result in productive lytic replication. Given their co-existence with humans and shared epigenetic silencing, we asked if HERV expression might be linked to lytic activation of human gammaherpesviruses. We found ERVW-1 mRNA, encoding the functional HERV-W envelope protein Syncytin-1, along with other repeat class elements, to be elevated upon lytic activation of EBV. Knockdown/knockout of ERVW-1 reduced lytic activation of EBV and KSHV in response to various lytic cycle triggers. In this regard, reduced expression of immediate early proteins ZEBRA and RTA for EBV and KSHV, respectively, places Syncytin-1’s influence on lytic activation mechanistically upstream of the latent-to-lytic switch. Conversely, overexpression of Syncytin-1 enhanced lytic activation of EBV and KSHV in response to lytic triggers, though this was not sufficient to induce lytic activation in the absence of such triggers. Syncytin-1 is expressed in replicating B cell blasts and lymphoma-derived B cell lines where it appears to contribute to cell cycle progression. Together, human gammaherpesviruses and B cells appear to have adapted a dependency on Syncytin-1 that facilitates the ability of EBV and KSHV to activate lytic replication from latency, while promoting viral persistence during latency by contributing to B cell proliferation. |
format | Online Article Text |
id | pubmed-8381357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83813572021-08-24 An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles Frey, Tiffany R. Akinyemi, Ibukun A. Burton, Eric M. Bhaduri-McIntosh, Sumita McIntosh, Michael T. Front Microbiol Microbiology Human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) persist as life-long infections alternating between latency and lytic replication. Human endogenous retroviruses (HERVs), via integration into the host genome, represent genetic remnants of ancient retroviral infections. Both show similar epigenetic silencing while dormant, but can reactivate in response to cell signaling cues or triggers that, for gammaherpesviruses, result in productive lytic replication. Given their co-existence with humans and shared epigenetic silencing, we asked if HERV expression might be linked to lytic activation of human gammaherpesviruses. We found ERVW-1 mRNA, encoding the functional HERV-W envelope protein Syncytin-1, along with other repeat class elements, to be elevated upon lytic activation of EBV. Knockdown/knockout of ERVW-1 reduced lytic activation of EBV and KSHV in response to various lytic cycle triggers. In this regard, reduced expression of immediate early proteins ZEBRA and RTA for EBV and KSHV, respectively, places Syncytin-1’s influence on lytic activation mechanistically upstream of the latent-to-lytic switch. Conversely, overexpression of Syncytin-1 enhanced lytic activation of EBV and KSHV in response to lytic triggers, though this was not sufficient to induce lytic activation in the absence of such triggers. Syncytin-1 is expressed in replicating B cell blasts and lymphoma-derived B cell lines where it appears to contribute to cell cycle progression. Together, human gammaherpesviruses and B cells appear to have adapted a dependency on Syncytin-1 that facilitates the ability of EBV and KSHV to activate lytic replication from latency, while promoting viral persistence during latency by contributing to B cell proliferation. Frontiers Media S.A. 2021-08-09 /pmc/articles/PMC8381357/ /pubmed/34434177 http://dx.doi.org/10.3389/fmicb.2021.708404 Text en Copyright © 2021 Frey, Akinyemi, Burton, Bhaduri-McIntosh and McIntosh. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Frey, Tiffany R. Akinyemi, Ibukun A. Burton, Eric M. Bhaduri-McIntosh, Sumita McIntosh, Michael T. An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles |
title | An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles |
title_full | An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles |
title_fullStr | An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles |
title_full_unstemmed | An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles |
title_short | An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles |
title_sort | ancestral retrovirus envelope protein regulates persistent gammaherpesvirus lifecycles |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381357/ https://www.ncbi.nlm.nih.gov/pubmed/34434177 http://dx.doi.org/10.3389/fmicb.2021.708404 |
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