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Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection
Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for hig...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518280/ https://www.ncbi.nlm.nih.gov/pubmed/35976035 http://dx.doi.org/10.1080/22221751.2022.2114849 |
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author | Jiang, Xinyi Chang, Le Yan, Ying Ji, Huimin Sun, Huizhen Xiao, Yingzi Song, Shi Feng, Kaihao Nuermaimaiti, Abudulimutailipu Wang, Lunan |
author_facet | Jiang, Xinyi Chang, Le Yan, Ying Ji, Huimin Sun, Huizhen Xiao, Yingzi Song, Shi Feng, Kaihao Nuermaimaiti, Abudulimutailipu Wang, Lunan |
author_sort | Jiang, Xinyi |
collection | PubMed |
description | Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for high-frequency mutations in transmembrane domain (TMD) of S protein in the OBI population. Plasmids with TMD high-frequency mutations were constructed, in vivo and in vitro functional experiments were performed to investigate possible molecular mechanisms of OBI occurrence. We found 22 high-frequency TMD mutations in genotype B OBI strains. Among them, five mutations can lead to impairment of HBsAg secretion; seven mutations had accumulated intracellular HBsAg while extracellular HBsAg didn’t decrease compared to wildtype. This study chose C85R from TMD2, F220C, and F220Y from TMD4 for further exploration. Protein structure predication showed these three mutant HBsAg displayed changed hydrophilic properties and tended to accumulate in the phospholipid bilayer of cell membrane. Mutant HBsAg’s secretion disorder may induce OBI. On the other hand, V168A + V177A from TMD3 expressed increased HBsAg both in intracellular and extracellular levels. This mutation had most unstable natural conformation and may be inclined to transition into V177A or V168A + S174N + V177A. These three mutations were more prone to mixed infection, presenting a state of coexistence, thus approaching the impaired secretion pattern of OBI. This study demonstrated TMD mutations could contribute to the occurrence of OBI and provided a theoretical basis for OBI study and the functional cure of chronic hepatitis B virus infection. |
format | Online Article Text |
id | pubmed-9518280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-95182802022-09-29 Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection Jiang, Xinyi Chang, Le Yan, Ying Ji, Huimin Sun, Huizhen Xiao, Yingzi Song, Shi Feng, Kaihao Nuermaimaiti, Abudulimutailipu Wang, Lunan Emerg Microbes Infect Hepatitis Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for high-frequency mutations in transmembrane domain (TMD) of S protein in the OBI population. Plasmids with TMD high-frequency mutations were constructed, in vivo and in vitro functional experiments were performed to investigate possible molecular mechanisms of OBI occurrence. We found 22 high-frequency TMD mutations in genotype B OBI strains. Among them, five mutations can lead to impairment of HBsAg secretion; seven mutations had accumulated intracellular HBsAg while extracellular HBsAg didn’t decrease compared to wildtype. This study chose C85R from TMD2, F220C, and F220Y from TMD4 for further exploration. Protein structure predication showed these three mutant HBsAg displayed changed hydrophilic properties and tended to accumulate in the phospholipid bilayer of cell membrane. Mutant HBsAg’s secretion disorder may induce OBI. On the other hand, V168A + V177A from TMD3 expressed increased HBsAg both in intracellular and extracellular levels. This mutation had most unstable natural conformation and may be inclined to transition into V177A or V168A + S174N + V177A. These three mutations were more prone to mixed infection, presenting a state of coexistence, thus approaching the impaired secretion pattern of OBI. This study demonstrated TMD mutations could contribute to the occurrence of OBI and provided a theoretical basis for OBI study and the functional cure of chronic hepatitis B virus infection. Taylor & Francis 2022-09-21 /pmc/articles/PMC9518280/ /pubmed/35976035 http://dx.doi.org/10.1080/22221751.2022.2114849 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Hepatitis Jiang, Xinyi Chang, Le Yan, Ying Ji, Huimin Sun, Huizhen Xiao, Yingzi Song, Shi Feng, Kaihao Nuermaimaiti, Abudulimutailipu Wang, Lunan Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection |
title | Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection |
title_full | Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection |
title_fullStr | Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection |
title_full_unstemmed | Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection |
title_short | Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection |
title_sort | role of s protein transmembrane domain mutations in the development of occult hepatitis b virus infection |
topic | Hepatitis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518280/ https://www.ncbi.nlm.nih.gov/pubmed/35976035 http://dx.doi.org/10.1080/22221751.2022.2114849 |
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