Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients

Autores
Gauder, Catalina; Mojsiejczuk, Laura Noelia; Tadey, Luciana; Mammana, Lilia; Bouzas, Maria Belen; Campos, Rodolfo Hector; Flichman, Diego Martin
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103 IU/ml (group A) or > 103 IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9 × 10−4 ± 1.3 × 10−4) than group B (2.7 × 10−4 ± 7.4 × 10−5 substitution/site/year, p < .001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.
Fil: Gauder, Catalina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina
Fil: Mojsiejczuk, Laura Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tadey, Luciana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Bouzas, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Materia
EVOLUTION
HEPATITIS B VIRUS
LOW REPLICATIVE PATIENTS
NUCLEOTIDE SUBSTITUTION RATE
VIRAL LOAD
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/112196
Acceder
id CONICETDig_86d6f70b1390dd2d0c75bc756417ba54
oai_identifier_str oai:ri.conicet.gov.ar:11336/112196
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patientsGauder, CatalinaMojsiejczuk, Laura NoeliaTadey, LucianaMammana, LiliaBouzas, Maria BelenCampos, Rodolfo HectorFlichman, Diego MartinEVOLUTIONHEPATITIS B VIRUSLOW REPLICATIVE PATIENTSNUCLEOTIDE SUBSTITUTION RATEVIRAL LOADhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103 IU/ml (group A) or > 103 IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9 × 10−4 ± 1.3 × 10−4) than group B (2.7 × 10−4 ± 7.4 × 10−5 substitution/site/year, p < .001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.Fil: Gauder, Catalina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Mojsiejczuk, Laura Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tadey, Luciana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bouzas, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaElsevier Science2019-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112196Gauder, Catalina; Mojsiejczuk, Laura Noelia; Tadey, Luciana; Mammana, Lilia; Bouzas, Maria Belen; et al.; Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients; Elsevier Science; Infection, Genetics and Evolution; 67; 1-2019; 17-221567-1348CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1567134818305185?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/J.MEEGID.2018.10.017info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:42Zoai:ri.conicet.gov.ar:11336/112196instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:18:43.231CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
title Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
spellingShingle Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
Gauder, Catalina
EVOLUTION
HEPATITIS B VIRUS
LOW REPLICATIVE PATIENTS
NUCLEOTIDE SUBSTITUTION RATE
VIRAL LOAD
title_short Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
title_full Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
title_fullStr Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
title_full_unstemmed Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
title_sort Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients
dc.creator.none.fl_str_mv Gauder, Catalina
Mojsiejczuk, Laura Noelia
Tadey, Luciana
Mammana, Lilia
Bouzas, Maria Belen
Campos, Rodolfo Hector
Flichman, Diego Martin
author Gauder, Catalina
author_facet Gauder, Catalina
Mojsiejczuk, Laura Noelia
Tadey, Luciana
Mammana, Lilia
Bouzas, Maria Belen
Campos, Rodolfo Hector
Flichman, Diego Martin
author_role author
author2 Mojsiejczuk, Laura Noelia
Tadey, Luciana
Mammana, Lilia
Bouzas, Maria Belen
Campos, Rodolfo Hector
Flichman, Diego Martin
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv EVOLUTION
HEPATITIS B VIRUS
LOW REPLICATIVE PATIENTS
NUCLEOTIDE SUBSTITUTION RATE
VIRAL LOAD
topic EVOLUTION
HEPATITIS B VIRUS
LOW REPLICATIVE PATIENTS
NUCLEOTIDE SUBSTITUTION RATE
VIRAL LOAD
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103 IU/ml (group A) or > 103 IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9 × 10−4 ± 1.3 × 10−4) than group B (2.7 × 10−4 ± 7.4 × 10−5 substitution/site/year, p < .001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.
Fil: Gauder, Catalina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina
Fil: Mojsiejczuk, Laura Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tadey, Luciana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Bouzas, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
description Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103 IU/ml (group A) or > 103 IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9 × 10−4 ± 1.3 × 10−4) than group B (2.7 × 10−4 ± 7.4 × 10−5 substitution/site/year, p < .001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.
publishDate 2019
dc.date.none.fl_str_mv 2019-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/112196
Gauder, Catalina; Mojsiejczuk, Laura Noelia; Tadey, Luciana; Mammana, Lilia; Bouzas, Maria Belen; et al.; Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients; Elsevier Science; Infection, Genetics and Evolution; 67; 1-2019; 17-22
1567-1348
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112196
identifier_str_mv Gauder, Catalina; Mojsiejczuk, Laura Noelia; Tadey, Luciana; Mammana, Lilia; Bouzas, Maria Belen; et al.; Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients; Elsevier Science; Infection, Genetics and Evolution; 67; 1-2019; 17-22
1567-1348
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1567134818305185?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/J.MEEGID.2018.10.017
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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