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The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31
The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, S...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599729/ https://www.ncbi.nlm.nih.gov/pubmed/32992873 http://dx.doi.org/10.3390/pathogens9100786 |
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author | Gibson, Ryan T. Androphy, Elliot J. |
author_facet | Gibson, Ryan T. Androphy, Elliot J. |
author_sort | Gibson, Ryan T. |
collection | PubMed |
description | The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication. |
format | Online Article Text |
id | pubmed-7599729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75997292020-11-01 The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 Gibson, Ryan T. Androphy, Elliot J. Pathogens Article The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication. MDPI 2020-09-25 /pmc/articles/PMC7599729/ /pubmed/32992873 http://dx.doi.org/10.3390/pathogens9100786 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gibson, Ryan T. Androphy, Elliot J. The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 |
title | The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 |
title_full | The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 |
title_fullStr | The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 |
title_full_unstemmed | The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 |
title_short | The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31 |
title_sort | smc5/6 complex represses the replicative program of high-risk human papillomavirus type 31 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599729/ https://www.ncbi.nlm.nih.gov/pubmed/32992873 http://dx.doi.org/10.3390/pathogens9100786 |
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