Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region

Detalhes bibliográficos
Autor(a) principal: Araujo, Natalia M.
Data de Publicação: 2020
Outros Autores: Teles, Sheila A., Spitz, Natália
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/45711
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Melecular. Rio de Janeiro, RJ, Brasil.
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spelling Araujo, Natalia M.Teles, Sheila A.Spitz, Natália2021-01-15T13:08:54Z2021-01-15T13:08:54Z2020ARAUJO, Natalia M.; TELES, Sheila A.; SPITZ, Natália. Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region. Frontiers in Microbiology, v. 11, Article 616023, p. 1-22, Dec. 2020.1664-302Xhttps://www.arca.fiocruz.br/handle/icict/4571110.3389/fmicb.2020.616023engFrontiers MediaVírus da Hepatite BGenótiposMutaçãoFuga imunológicaResistência antiviralCarcinoma hepatocelularEvolução do HBVSeleção naturalHepatitis B virusGenotypesMutationImmune escapeAntiviral resistanceHepatocellular carcinomaHBV evolutionNatural selectionComprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Regioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Melecular. Rio de Janeiro, RJ, Brasil.Universidade Federal de Goiás. Faculdade de Enfermagem. Goiânia, GO, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Melecular. Rio de Janeiro, RJ, Brasil.Hepatitis B virus (HBV) is a highly variable DNA virus due to its unique life cycle, which involves an error-prone reverse transcriptase. The high substitution rate drives the evolution of HBV by generating genetic variants upon which selection operates. HBV mutants with clinical implications have been documented worldwide, indicating the potential for spreading and developing their own epidemiology. However, the prevalence of such mutants among the different HBV genotypes and subgenotypes has not been systematically analyzed. In the current study, we performed large-scale analysis of 6,479 full-length HBV genome sequences from genotypes A-H, with the aim of gaining comprehensive insights into the relationships of relevant mutations associated with immune escape, antiviral resistance and hepatocellular carcinoma (HCC) development with HBV (sub)genotypes and geographic regions. Immune escape mutations were detected in 10.7% of the sequences, the most common being I/T126S (1.8%), G145R (1.2%), M133T (1.2%), and Q129R (1.0%). HBV genotype B showed the highest rate of escape mutations (14.7%) while genotype H had no mutations (P < 0.001). HCC-associated mutations were detected in 33.7% of the sequences, with significantly higher frequency of C1653T, T1753V and A1762T/G1764A in genotype G than C (P < 0.001). The overall frequencies of lamivudine-, telbivudine-, adefovir-, and entecavir-resistant mutants were 7.3, 7.2, 0.5, and 0.2%, respectively, while only 0.05% showed reduced susceptibility to tenofovir. In particular, the highest frequency of lamivudine-resistant mutations was observed in genotype G and the lowest frequency in genotype E (32.5 and 0.3%; P < 0.001). The prevalence of HBV mutants was also biased by geographic location, with North America identified as one of the regions with the highest rates of immune escape, antiviral resistance, and HCC-associated mutants. The collective findings were discussed in light of natural selection and the known characteristics of HBV (sub)genotypes. Our data provide relevant information on the prevalence of clinically relevant HBV mutations, which may contribute to further improvement of diagnostic procedures, immunization programs, therapeutic protocols, and disease prognosis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/45711/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALNataliaMAraujo_NataliaSpitz_etal_IOC_2020.pdfNataliaMAraujo_NataliaSpitz_etal_IOC_2020.pdfapplication/pdf3218136https://www.arca.fiocruz.br/bitstream/icict/45711/2/NataliaMAraujo_NataliaSpitz_etal_IOC_2020.pdfe36828ac71323795804986df9a13eb35MD52TEXTNataliaMAraujo_NataliaSpitz_etal_IOC_2020.pdf.txtNataliaMAraujo_NataliaSpitz_etal_IOC_2020.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
title Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
spellingShingle Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
Araujo, Natalia M.
Vírus da Hepatite B
Genótipos
Mutação
Fuga imunológica
Resistência antiviral
Carcinoma hepatocelular
Evolução do HBV
Seleção natural
Hepatitis B virus
Genotypes
Mutation
Immune escape
Antiviral resistance
Hepatocellular carcinoma
HBV evolution
Natural selection
title_short Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
title_full Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
title_fullStr Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
title_full_unstemmed Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
title_sort Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region
author Araujo, Natalia M.
author_facet Araujo, Natalia M.
Teles, Sheila A.
Spitz, Natália
author_role author
author2 Teles, Sheila A.
Spitz, Natália
author2_role author
author
dc.contributor.author.fl_str_mv Araujo, Natalia M.
Teles, Sheila A.
Spitz, Natália
dc.subject.other.pt_BR.fl_str_mv Vírus da Hepatite B
Genótipos
Mutação
Fuga imunológica
Resistência antiviral
Carcinoma hepatocelular
Evolução do HBV
Seleção natural
topic Vírus da Hepatite B
Genótipos
Mutação
Fuga imunológica
Resistência antiviral
Carcinoma hepatocelular
Evolução do HBV
Seleção natural
Hepatitis B virus
Genotypes
Mutation
Immune escape
Antiviral resistance
Hepatocellular carcinoma
HBV evolution
Natural selection
dc.subject.en.pt_BR.fl_str_mv Hepatitis B virus
Genotypes
Mutation
Immune escape
Antiviral resistance
Hepatocellular carcinoma
HBV evolution
Natural selection
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Melecular. Rio de Janeiro, RJ, Brasil.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2021-01-15T13:08:54Z
dc.date.available.fl_str_mv 2021-01-15T13:08:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv ARAUJO, Natalia M.; TELES, Sheila A.; SPITZ, Natália. Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region. Frontiers in Microbiology, v. 11, Article 616023, p. 1-22, Dec. 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/45711
dc.identifier.issn.pt_BR.fl_str_mv 1664-302X
dc.identifier.doi.none.fl_str_mv 10.3389/fmicb.2020.616023
identifier_str_mv ARAUJO, Natalia M.; TELES, Sheila A.; SPITZ, Natália. Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region. Frontiers in Microbiology, v. 11, Article 616023, p. 1-22, Dec. 2020.
1664-302X
10.3389/fmicb.2020.616023
url https://www.arca.fiocruz.br/handle/icict/45711
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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