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Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins

Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins. S protein drives virion and subviral particle secretion, whereas L protein inhibits subviral particle secretion but coordinates virion morphogenesis. We previously found that preventing S protein ex...

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Autores principales: Zhang, Jing, Wang, Yongxiang, Fu, Shuwen, Yuan, Quan, Wang, Qianru, Xia, Ningshao, Wen, Yumei, Li, Jisu, Tong, Shuping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065445/
https://www.ncbi.nlm.nih.gov/pubmed/33918367
http://dx.doi.org/10.3390/v13040613
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author Zhang, Jing
Wang, Yongxiang
Fu, Shuwen
Yuan, Quan
Wang, Qianru
Xia, Ningshao
Wen, Yumei
Li, Jisu
Tong, Shuping
author_facet Zhang, Jing
Wang, Yongxiang
Fu, Shuwen
Yuan, Quan
Wang, Qianru
Xia, Ningshao
Wen, Yumei
Li, Jisu
Tong, Shuping
author_sort Zhang, Jing
collection PubMed
description Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins. S protein drives virion and subviral particle secretion, whereas L protein inhibits subviral particle secretion but coordinates virion morphogenesis. We previously found that preventing S protein expression from a subgenomic construct eliminated M protein. The present study further examined impact of S protein on L and M proteins. Mutations were introduced to subgenomic construct of genotype A or 1.1 mer replication construct of genotype A or D, and viral proteins were analyzed from transfected Huh7 cells. Mutating S gene ATG to prevent expression of full-length S protein eliminated M protein, reduced intracellular level of L protein despite its blocked secretion, and generated a truncated S protein through translation initiation from a downstream ATG. Truncated S protein was secretion deficient and could inhibit secretion of L, M, S proteins from wild-type constructs. Providing full-length S protein in trans rescued L protein secretion and increased its intracellular level from mutants of lost S gene ATG. Lost core protein expression reduced all the three envelope proteins. In conclusion, full-length S protein could sustain intracellular and extracellular L and M proteins, while truncated S protein could block subviral particle secretion.
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spelling pubmed-80654452021-04-25 Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins Zhang, Jing Wang, Yongxiang Fu, Shuwen Yuan, Quan Wang, Qianru Xia, Ningshao Wen, Yumei Li, Jisu Tong, Shuping Viruses Article Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins. S protein drives virion and subviral particle secretion, whereas L protein inhibits subviral particle secretion but coordinates virion morphogenesis. We previously found that preventing S protein expression from a subgenomic construct eliminated M protein. The present study further examined impact of S protein on L and M proteins. Mutations were introduced to subgenomic construct of genotype A or 1.1 mer replication construct of genotype A or D, and viral proteins were analyzed from transfected Huh7 cells. Mutating S gene ATG to prevent expression of full-length S protein eliminated M protein, reduced intracellular level of L protein despite its blocked secretion, and generated a truncated S protein through translation initiation from a downstream ATG. Truncated S protein was secretion deficient and could inhibit secretion of L, M, S proteins from wild-type constructs. Providing full-length S protein in trans rescued L protein secretion and increased its intracellular level from mutants of lost S gene ATG. Lost core protein expression reduced all the three envelope proteins. In conclusion, full-length S protein could sustain intracellular and extracellular L and M proteins, while truncated S protein could block subviral particle secretion. MDPI 2021-04-02 /pmc/articles/PMC8065445/ /pubmed/33918367 http://dx.doi.org/10.3390/v13040613 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 Article
Zhang, Jing
Wang, Yongxiang
Fu, Shuwen
Yuan, Quan
Wang, Qianru
Xia, Ningshao
Wen, Yumei
Li, Jisu
Tong, Shuping
Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins
title Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins
title_full Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins
title_fullStr Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins
title_full_unstemmed Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins
title_short Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins
title_sort role of small envelope protein in sustaining the intracellular and extracellular levels of hepatitis b virus large and middle envelope proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065445/
https://www.ncbi.nlm.nih.gov/pubmed/33918367
http://dx.doi.org/10.3390/v13040613
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