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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...

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Autores principales: Gibson, Ryan T., Androphy, Elliot J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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