Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models

Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV infection is still an enigma. Here, we reported that 7.33% (11/150) isolates of CHB patients had MHBs start codon mutations compared w...

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Autores principales:	Junyu Lin, Jing Li, Peilin Xie, Yue Han, Demin Yu, Jia Chen, Xinxin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	hepatitis b virus middle surface antigen chronic infection start codon mutation cytokines Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/7db3826e85374af18c7fce84b2131fec
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spelling	oai:doaj.org-article:7db3826e85374af18c7fce84b2131fec2021-11-26T11:19:49ZHepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models2150-55942150-560810.1080/21505594.2021.1999130https://doaj.org/article/7db3826e85374af18c7fce84b2131fec2021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2021.1999130https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV infection is still an enigma. Here, we reported that 7.33% (11/150) isolates of CHB patients had MHBs start codon mutations compared with 0.00% (0/146) in acute hepatitis B (AHB) patients. Interestingly, MHBs loss accounted for 11.88% (126/1061) isolates from NCBI GenBank, compared with 0.09% (1/1061) and 0.00% (0/1061) for HBV large surface antigen (LHBs) loss and HBV small surface antigen (SHBs) loss, respectively. One persistent HBV clone of genotype B (B56, MHBs loss) from a CHB patient was hydrodynamically injected into BALB/c mice. B56 persisted for >70 weeks in BALB/c mice, whereas B56 with restored MHBs (B56M+) was quickly cleared within 28 days. Serum cytokine assays demonstrated that CXCL1, CXCL2, IL-6 and IL-33 were significantly increased during rapid HBV clearance in B56M+ mice. Furthermore, the enhancers and promoters of B56 were proved to be required for B56 persistence in mice. Ablating MHBs expression improved the persistence of a new clone (HBV1.3, genotype B) which was recreated by using enhancers and promoters of B56. These data demonstrated that MHBs deletion can promote the persistence of specific HBV variants in a hydrodynamic mouse model. MHBs re-expression restored a rapid clearance of HBV, which was accompanied by cytokine responses including the elevation of CXCL1, CXCL2, IL-6 and IL-33.Junyu LinJing LiPeilin XieYue HanDemin YuJia ChenXinxin ZhangTaylor & Francis Grouparticlehepatitis b virusmiddle surface antigenchronic infectionstart codon mutationcytokinesInfectious and parasitic diseasesRC109-216ENVirulence, Vol 12, Iss 1, Pp 2868-2882 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatitis b virus middle surface antigen chronic infection start codon mutation cytokines Infectious and parasitic diseases RC109-216
spellingShingle	hepatitis b virus middle surface antigen chronic infection start codon mutation cytokines Infectious and parasitic diseases RC109-216 Junyu Lin Jing Li Peilin Xie Yue Han Demin Yu Jia Chen Xinxin Zhang Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models
description	Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV infection is still an enigma. Here, we reported that 7.33% (11/150) isolates of CHB patients had MHBs start codon mutations compared with 0.00% (0/146) in acute hepatitis B (AHB) patients. Interestingly, MHBs loss accounted for 11.88% (126/1061) isolates from NCBI GenBank, compared with 0.09% (1/1061) and 0.00% (0/1061) for HBV large surface antigen (LHBs) loss and HBV small surface antigen (SHBs) loss, respectively. One persistent HBV clone of genotype B (B56, MHBs loss) from a CHB patient was hydrodynamically injected into BALB/c mice. B56 persisted for >70 weeks in BALB/c mice, whereas B56 with restored MHBs (B56M+) was quickly cleared within 28 days. Serum cytokine assays demonstrated that CXCL1, CXCL2, IL-6 and IL-33 were significantly increased during rapid HBV clearance in B56M+ mice. Furthermore, the enhancers and promoters of B56 were proved to be required for B56 persistence in mice. Ablating MHBs expression improved the persistence of a new clone (HBV1.3, genotype B) which was recreated by using enhancers and promoters of B56. These data demonstrated that MHBs deletion can promote the persistence of specific HBV variants in a hydrodynamic mouse model. MHBs re-expression restored a rapid clearance of HBV, which was accompanied by cytokine responses including the elevation of CXCL1, CXCL2, IL-6 and IL-33.
format	article
author	Junyu Lin Jing Li Peilin Xie Yue Han Demin Yu Jia Chen Xinxin Zhang
author_facet	Junyu Lin Jing Li Peilin Xie Yue Han Demin Yu Jia Chen Xinxin Zhang
author_sort	Junyu Lin
title	Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models
title_short	Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models
title_full	Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models
title_fullStr	Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models
title_full_unstemmed	Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models
title_sort	hepatitis b virus middle surface antigen loss promotes clinical variant persistence in mouse models
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/7db3826e85374af18c7fce84b2131fec
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_version_	1718409481745858560

Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models

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