A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion

Abstract Background The virion secretion mechanism of human hepatitis B virus (HBV) remains to be investigated. In our current study, we characterized a reverse transcriptase mutant, which changed from the YMDD motif to YMHA. We noted that this mutant YMHA secreted no virions in the medium. Because...

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Autores principales:	Chih-Hsu Chang, Shu-Fan Chou, Chiaho Shih
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hepatitis B virus HBV Virion secretion Envelope protein Small loop Proline substitution Medicine R
Acceso en línea:	https://doaj.org/article/70350f114ccb4ddca3c6ea7e42a31ef1
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spelling	oai:doaj.org-article:70350f114ccb4ddca3c6ea7e42a31ef12021-12-05T12:10:35ZA nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion10.1186/s12929-021-00780-01423-0127https://doaj.org/article/70350f114ccb4ddca3c6ea7e42a31ef12021-12-01T00:00:00Zhttps://doi.org/10.1186/s12929-021-00780-0https://doaj.org/toc/1423-0127Abstract Background The virion secretion mechanism of human hepatitis B virus (HBV) remains to be investigated. In our current study, we characterized a reverse transcriptase mutant, which changed from the YMDD motif to YMHA. We noted that this mutant YMHA secreted no virions in the medium. Because of the overlapping open reading frame (ORF) between the polymerase and the envelope genes, the lack of virion secretion is likely due to corresponding concurrent mutations in a small loop of the envelope protein (HBsAg, HBV surface antigen). In literature, small loop mutations are thought to affect virion secretion of hepatitis delta virus (HDV), but not HBV. Methods Here, we revisited the relationship between the small loop and virion secretion by site-directed mutagenesis and native agarose gel electrophoresis. Results A proline substitution at residue 196 or 198 in the small loop blocked both HBV genome-containing and genome-free virion secretion, but not the secretion of 22-nm HBsAg subviral particles. Surprisingly, a leucine substitution at residue 196 enhanced genome-containing virion secretion. It is also intriguing that a proline-197, sandwiched by residue 196 and 198, exhibited no apparent defect in secreted virions, with or without containing an HBV genome. By complementation assay, we demonstrated that the wild type small envelope protein alone is sufficient to rescue the virion secretion defect of a small loop mutant M198P. Conclusions The effect of the small loop mutation of HBV small envelope protein on virion secretion is position-dependent. It warrants further investigation how the small loop of HBsAg plays a subtle role in HBV morphogenesis and secretion of virions with or without containing an HBV genome.Chih-Hsu ChangShu-Fan ChouChiaho ShihBMCarticleHepatitis B virusHBVVirion secretionEnvelope proteinSmall loopProline substitutionMedicineRENJournal of Biomedical Science, Vol 28, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatitis B virus HBV Virion secretion Envelope protein Small loop Proline substitution Medicine R
spellingShingle	Hepatitis B virus HBV Virion secretion Envelope protein Small loop Proline substitution Medicine R Chih-Hsu Chang Shu-Fan Chou Chiaho Shih A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion
description	Abstract Background The virion secretion mechanism of human hepatitis B virus (HBV) remains to be investigated. In our current study, we characterized a reverse transcriptase mutant, which changed from the YMDD motif to YMHA. We noted that this mutant YMHA secreted no virions in the medium. Because of the overlapping open reading frame (ORF) between the polymerase and the envelope genes, the lack of virion secretion is likely due to corresponding concurrent mutations in a small loop of the envelope protein (HBsAg, HBV surface antigen). In literature, small loop mutations are thought to affect virion secretion of hepatitis delta virus (HDV), but not HBV. Methods Here, we revisited the relationship between the small loop and virion secretion by site-directed mutagenesis and native agarose gel electrophoresis. Results A proline substitution at residue 196 or 198 in the small loop blocked both HBV genome-containing and genome-free virion secretion, but not the secretion of 22-nm HBsAg subviral particles. Surprisingly, a leucine substitution at residue 196 enhanced genome-containing virion secretion. It is also intriguing that a proline-197, sandwiched by residue 196 and 198, exhibited no apparent defect in secreted virions, with or without containing an HBV genome. By complementation assay, we demonstrated that the wild type small envelope protein alone is sufficient to rescue the virion secretion defect of a small loop mutant M198P. Conclusions The effect of the small loop mutation of HBV small envelope protein on virion secretion is position-dependent. It warrants further investigation how the small loop of HBsAg plays a subtle role in HBV morphogenesis and secretion of virions with or without containing an HBV genome.
format	article
author	Chih-Hsu Chang Shu-Fan Chou Chiaho Shih
author_facet	Chih-Hsu Chang Shu-Fan Chou Chiaho Shih
author_sort	Chih-Hsu Chang
title	A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion
title_short	A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion
title_full	A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion
title_fullStr	A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion
title_full_unstemmed	A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion
title_sort	nuanced role of the small loop of hepatitis b virus small envelope protein in virion morphogenesis and secretion
publisher	BMC
publishDate	2021
url	https://doaj.org/article/70350f114ccb4ddca3c6ea7e42a31ef1
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A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion

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