Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients

Abstract Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5′ end of HBX in CI patients and compared it with that of patie...

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Autores principales:	Maria Francesca Cortese, Carolina González, Josep Gregori, Rosario Casillas, Luca Carioti, Mercedes Guerrero-Murillo, Mar Riveiro-Barciela, Cristina Godoy, Sara Sopena, Marçal Yll, Josep Quer, Ariadna Rando, Rosa Lopez-Martinez, Beatriz Pacín Ruiz, Selene García-García, Rafael Esteban-Mur, David Tabernero, Maria Buti, Francisco Rodríguez-Frías
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bae6b63e6994cb78433411466be5879
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spelling	oai:doaj.org-article:8bae6b63e6994cb78433411466be58792021-12-02T12:11:28ZSophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients10.1038/s41598-021-83762-42045-2322https://doaj.org/article/8bae6b63e6994cb78433411466be58792021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83762-4https://doaj.org/toc/2045-2322Abstract Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5′ end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p < 0.05). A genotype D-specific pattern of mutations (A12S/P33S/P46S/T36D-G) was identified in CI (median frequency, 81.7%), which determined a reduction in HBV DNA release of up to 1.5 log in vitro. CI patients showed a more complex and conserved viral quasispecies than the other groups. The genotype-specific pattern of mutations could partially explain the low viremia observed in these patients.Maria Francesca CorteseCarolina GonzálezJosep GregoriRosario CasillasLuca CariotiMercedes Guerrero-MurilloMar Riveiro-BarcielaCristina GodoySara SopenaMarçal YllJosep QuerAriadna RandoRosa Lopez-MartinezBeatriz Pacín RuizSelene García-GarcíaRafael Esteban-MurDavid TaberneroMaria ButiFrancisco Rodríguez-FríasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Francesca Cortese Carolina González Josep Gregori Rosario Casillas Luca Carioti Mercedes Guerrero-Murillo Mar Riveiro-Barciela Cristina Godoy Sara Sopena Marçal Yll Josep Quer Ariadna Rando Rosa Lopez-Martinez Beatriz Pacín Ruiz Selene García-García Rafael Esteban-Mur David Tabernero Maria Buti Francisco Rodríguez-Frías Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
description	Abstract Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5′ end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p < 0.05). A genotype D-specific pattern of mutations (A12S/P33S/P46S/T36D-G) was identified in CI (median frequency, 81.7%), which determined a reduction in HBV DNA release of up to 1.5 log in vitro. CI patients showed a more complex and conserved viral quasispecies than the other groups. The genotype-specific pattern of mutations could partially explain the low viremia observed in these patients.
format	article
author	Maria Francesca Cortese Carolina González Josep Gregori Rosario Casillas Luca Carioti Mercedes Guerrero-Murillo Mar Riveiro-Barciela Cristina Godoy Sara Sopena Marçal Yll Josep Quer Ariadna Rando Rosa Lopez-Martinez Beatriz Pacín Ruiz Selene García-García Rafael Esteban-Mur David Tabernero Maria Buti Francisco Rodríguez-Frías
author_facet	Maria Francesca Cortese Carolina González Josep Gregori Rosario Casillas Luca Carioti Mercedes Guerrero-Murillo Mar Riveiro-Barciela Cristina Godoy Sara Sopena Marçal Yll Josep Quer Ariadna Rando Rosa Lopez-Martinez Beatriz Pacín Ruiz Selene García-García Rafael Esteban-Mur David Tabernero Maria Buti Francisco Rodríguez-Frías
author_sort	Maria Francesca Cortese
title	Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
title_short	Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
title_full	Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
title_fullStr	Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
title_full_unstemmed	Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
title_sort	sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis b x gene of hbeag-ve chronically infected patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8bae6b63e6994cb78433411466be5879
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Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients

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