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SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation
Hepatitis B virus (HBV) replication is controlled by four promoters (preS1, preS2, Cp, and Xp) and two enhancers (EnhI and EnhII). EnhII stimulates Cp activity to regulate the transcriptions of precore, core, polymerase, and pregenomic RNAs, and therefore, EnhII/Cp is essential for the regulation of...
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/PMC7150879/ https://www.ncbi.nlm.nih.gov/pubmed/32121397 http://dx.doi.org/10.3390/v12030273 |
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author | Yang, Hua Mo, Jiayin Xiang, Qi Zhao, Peiyi Song, Yunting Yang, Ge Wu, Kailang Liu, Yingle Liu, Weiyong Wu, Jianguo |
author_facet | Yang, Hua Mo, Jiayin Xiang, Qi Zhao, Peiyi Song, Yunting Yang, Ge Wu, Kailang Liu, Yingle Liu, Weiyong Wu, Jianguo |
author_sort | Yang, Hua |
collection | PubMed |
description | Hepatitis B virus (HBV) replication is controlled by four promoters (preS1, preS2, Cp, and Xp) and two enhancers (EnhI and EnhII). EnhII stimulates Cp activity to regulate the transcriptions of precore, core, polymerase, and pregenomic RNAs, and therefore, EnhII/Cp is essential for the regulation of HBV replication. This study revealed a distinct mechanism underlying the suppression of EnhII/Cp activation and HBV replication. On the one hand, the sex determining region Y box2 (SOX2), a transcription factor, is induced by HBV. On the other hand, SOX2, in turn, represses the expression levels of HBV RNAs, HBV core-associated DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg), thereby playing an inhibitory role during HBV replication. Further studies indicated that SOX2 bound to the EnhII/Cp DNA and repressed the promoter activation. With the deletion of the high mobility group (HMG) domain, SOX2 loses the ability to repress EnhII/Cp activation, viral RNA transcription, HBV core-associated DNA replication, HBsAg and HBeAg production, as well as fails to enter the nucleus, demonstrating that the HMG domain is required for the SOX2-mediated repression of HBV replication. Moreover, SOX2 represses HBsAg and HBeAg secretion in BALB/c mice sera, and attenuates HBV 3.5 kb RNA transcription and hepatitis B virus core protein (HBc) production in the liver tissues, demonstrating that SOX2 suppresses HBV replication in mice. Furthermore, the results revealed that the HMG domain was required for SOX2-mediated repression of HBV replication in the mice. Taken together, the above facts indicate that SOX2 acts as a new host restriction factor to repress HBV replication by binding to the viral EnhII/Cp and inhibiting the promoter activation through the HMG domain. |
format | Online Article Text |
id | pubmed-7150879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71508792020-04-20 SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation Yang, Hua Mo, Jiayin Xiang, Qi Zhao, Peiyi Song, Yunting Yang, Ge Wu, Kailang Liu, Yingle Liu, Weiyong Wu, Jianguo Viruses Article Hepatitis B virus (HBV) replication is controlled by four promoters (preS1, preS2, Cp, and Xp) and two enhancers (EnhI and EnhII). EnhII stimulates Cp activity to regulate the transcriptions of precore, core, polymerase, and pregenomic RNAs, and therefore, EnhII/Cp is essential for the regulation of HBV replication. This study revealed a distinct mechanism underlying the suppression of EnhII/Cp activation and HBV replication. On the one hand, the sex determining region Y box2 (SOX2), a transcription factor, is induced by HBV. On the other hand, SOX2, in turn, represses the expression levels of HBV RNAs, HBV core-associated DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg), thereby playing an inhibitory role during HBV replication. Further studies indicated that SOX2 bound to the EnhII/Cp DNA and repressed the promoter activation. With the deletion of the high mobility group (HMG) domain, SOX2 loses the ability to repress EnhII/Cp activation, viral RNA transcription, HBV core-associated DNA replication, HBsAg and HBeAg production, as well as fails to enter the nucleus, demonstrating that the HMG domain is required for the SOX2-mediated repression of HBV replication. Moreover, SOX2 represses HBsAg and HBeAg secretion in BALB/c mice sera, and attenuates HBV 3.5 kb RNA transcription and hepatitis B virus core protein (HBc) production in the liver tissues, demonstrating that SOX2 suppresses HBV replication in mice. Furthermore, the results revealed that the HMG domain was required for SOX2-mediated repression of HBV replication in the mice. Taken together, the above facts indicate that SOX2 acts as a new host restriction factor to repress HBV replication by binding to the viral EnhII/Cp and inhibiting the promoter activation through the HMG domain. MDPI 2020-02-29 /pmc/articles/PMC7150879/ /pubmed/32121397 http://dx.doi.org/10.3390/v12030273 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 Yang, Hua Mo, Jiayin Xiang, Qi Zhao, Peiyi Song, Yunting Yang, Ge Wu, Kailang Liu, Yingle Liu, Weiyong Wu, Jianguo SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation |
title | SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation |
title_full | SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation |
title_fullStr | SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation |
title_full_unstemmed | SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation |
title_short | SOX2 Represses Hepatitis B Virus Replication by Binding to the Viral EnhII/Cp and Inhibiting the Promoter Activation |
title_sort | sox2 represses hepatitis b virus replication by binding to the viral enhii/cp and inhibiting the promoter activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150879/ https://www.ncbi.nlm.nih.gov/pubmed/32121397 http://dx.doi.org/10.3390/v12030273 |
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