Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence

Detalhes bibliográficos
Autor(a) principal: Ke, Ruian
Data de Publicação: 2018
Outros Autores: Li, Hui, Wang, Shuyi, Ding, Wenge, Ribeiro, Ruy M., Giorgi, Elena E, Bhattacharya, Tanmoy, Barnard, Richard J O, Hahn, Beatrice H, Shaw, George M, Perelson, Alan S
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/45067
Resumo: Copyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
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spelling Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistenceHepatitis C virusMathematical modelingPhylodynamic modelingVirus evolutionVirus persistenceCopyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).RNA viruses exist as a genetically diverse quasispecies with extraordinary ability to adapt to abrupt changes in the host environment. However, the molecular mechanisms that contribute to their rapid adaptation and persistence in vivo are not well studied. Here, we probe hepatitis C virus (HCV) persistence by analyzing clinical samples taken from subjects who were treated with a second-generation HCV protease inhibitor. Frequent longitudinal viral load determinations and large-scale single-genome sequence analyses revealed rapid antiviral resistance development, and surprisingly, dynamic turnover of dominant drug-resistant mutant populations long after treatment cessation. We fitted mathematical models to both the viral load and the viral sequencing data, and the results provided strong support for the critical roles that superinfection and cure of infected cells play in facilitating the rapid turnover and persistence of viral populations. More broadly, our results highlight the importance of considering viral dynamics and competition at the intracellular level in understanding rapid viral adaptation. Thus, we propose a theoretical framework integrating viral and molecular mechanisms to explain rapid viral evolution, resistance, and persistence despite antiviral treatment and host immune responses.National Academy of SciencesRepositório da Universidade de LisboaKe, RuianLi, HuiWang, ShuyiDing, WengeRibeiro, Ruy M.Giorgi, Elena EBhattacharya, TanmoyBarnard, Richard J OHahn, Beatrice HShaw, George MPerelson, Alan S2020-12-02T13:39:35Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/45067engPNAS July 24, 2018 115 (30) E7139-E71480027-842410.1073/pnas.18052671151091-6490info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:46:32Zoai:repositorio.ul.pt:10451/45067Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:57:33.069582Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
title Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
spellingShingle Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
Ke, Ruian
Hepatitis C virus
Mathematical modeling
Phylodynamic modeling
Virus evolution
Virus persistence
title_short Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
title_full Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
title_fullStr Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
title_full_unstemmed Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
title_sort Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
author Ke, Ruian
author_facet Ke, Ruian
Li, Hui
Wang, Shuyi
Ding, Wenge
Ribeiro, Ruy M.
Giorgi, Elena E
Bhattacharya, Tanmoy
Barnard, Richard J O
Hahn, Beatrice H
Shaw, George M
Perelson, Alan S
author_role author
author2 Li, Hui
Wang, Shuyi
Ding, Wenge
Ribeiro, Ruy M.
Giorgi, Elena E
Bhattacharya, Tanmoy
Barnard, Richard J O
Hahn, Beatrice H
Shaw, George M
Perelson, Alan S
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Ke, Ruian
Li, Hui
Wang, Shuyi
Ding, Wenge
Ribeiro, Ruy M.
Giorgi, Elena E
Bhattacharya, Tanmoy
Barnard, Richard J O
Hahn, Beatrice H
Shaw, George M
Perelson, Alan S
dc.subject.por.fl_str_mv Hepatitis C virus
Mathematical modeling
Phylodynamic modeling
Virus evolution
Virus persistence
topic Hepatitis C virus
Mathematical modeling
Phylodynamic modeling
Virus evolution
Virus persistence
description Copyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
2020-12-02T13:39:35Z
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.uri.fl_str_mv http://hdl.handle.net/10451/45067
url http://hdl.handle.net/10451/45067
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PNAS July 24, 2018 115 (30) E7139-E7148
0027-8424
10.1073/pnas.1805267115
1091-6490
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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