Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy...

Autores
Bolcic, Federico Martin; Laufer, Natalia Lorna; Torres, Carolina; Cassino, Lucila; Reynoso, Rita Paola; Quarleri, Jorge Fabian
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: The rate of non-response to pegylated interferon plus ribavirin (peg-IFN. +. RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5' untranslated (5'UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5'UTR may influence the viral lymphotropism. Methods: We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN. +. RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN. +. RBV non-responders and infected with HCV 1a. Results: Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p<0.001). The number of amino acid variations (mean ± SD) at the NS5A-ISDR domain was higher among HCV/HIV patients than HCV-monoinfected ones (1.80 ± 0.77 vs. 0.95 ± 1.05; p=0.009) but such difference was slightly lower when comparing NS5A-PKRBD sequences (2.47 ± 1.13 vs. 1.60 ± 1.57; p=0.06). No differences were found at the E2-PePHD (0 ± 0 vs. 0.2 ± 0.4). At intra-HIV coinfected patient level, only minor (HCV genetic analysis) or no (HCV substitution rate and quasispecies heterogeneity) changes were observed during therapy (basal, 24. h, 4. weeks, and 12. weeks). Conclusions: Among HCV-1a/HIV coinfected and HCV-monoinfected peg-IFN. +. RBV non-responder patients, the HCV variability at the 5'UTR, E2-PePHD and NS5A-PKRBD/ISDR domains was mostly comparable exhibiting a low number of variations. Four well-defined amino acid substitutions in NS5A-ISDR domain appeared most frequently when HIV coexists. The interferon-based therapy did not exert any effect in the variation, selection or diversity in the above mentioned HCV regions that could influence clinical responsiveness to IFN therapy.
Fil: Bolcic, Federico Martin. 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
Fil: Laufer, Natalia Lorna. 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
Fil: Torres, Carolina. 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. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Cassino, Lucila. 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
Fil: Reynoso, Rita Paola. 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
Fil: Quarleri, Jorge Fabian. 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
GENOTYPE 1A
HCV
HIV
PEGYLATED INTERFERON
RIBAVIRIN
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:11336/198538
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patientsBolcic, Federico MartinLaufer, Natalia LornaTorres, CarolinaCassino, LucilaReynoso, Rita PaolaQuarleri, Jorge FabianGENOTYPE 1AHCVHIVPEGYLATED INTERFERONRIBAVIRINhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: The rate of non-response to pegylated interferon plus ribavirin (peg-IFN. +. RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5' untranslated (5'UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5'UTR may influence the viral lymphotropism. Methods: We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN. +. RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN. +. RBV non-responders and infected with HCV 1a. Results: Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p<0.001). The number of amino acid variations (mean ± SD) at the NS5A-ISDR domain was higher among HCV/HIV patients than HCV-monoinfected ones (1.80 ± 0.77 vs. 0.95 ± 1.05; p=0.009) but such difference was slightly lower when comparing NS5A-PKRBD sequences (2.47 ± 1.13 vs. 1.60 ± 1.57; p=0.06). No differences were found at the E2-PePHD (0 ± 0 vs. 0.2 ± 0.4). At intra-HIV coinfected patient level, only minor (HCV genetic analysis) or no (HCV substitution rate and quasispecies heterogeneity) changes were observed during therapy (basal, 24. h, 4. weeks, and 12. weeks). Conclusions: Among HCV-1a/HIV coinfected and HCV-monoinfected peg-IFN. +. RBV non-responder patients, the HCV variability at the 5'UTR, E2-PePHD and NS5A-PKRBD/ISDR domains was mostly comparable exhibiting a low number of variations. Four well-defined amino acid substitutions in NS5A-ISDR domain appeared most frequently when HIV coexists. The interferon-based therapy did not exert any effect in the variation, selection or diversity in the above mentioned HCV regions that could influence clinical responsiveness to IFN therapy.Fil: Bolcic, Federico Martin. 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; ArgentinaFil: Laufer, Natalia Lorna. 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; ArgentinaFil: Torres, Carolina. 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. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cassino, Lucila. 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; ArgentinaFil: Reynoso, Rita Paola. 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; ArgentinaFil: Quarleri, Jorge Fabian. 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 Science2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/198538Bolcic, Federico Martin; Laufer, Natalia Lorna; Torres, Carolina; Cassino, Lucila; Reynoso, Rita Paola; et al.; Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients; Elsevier Science; Antiviral Research; 95; 2; 8-2012; 72-810166-3542CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0166354212001301info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2012.05.015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:47Zoai:ri.conicet.gov.ar:11336/198538instacron: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:34982025-09-03 10:00:47.997CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
title Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
spellingShingle Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
Bolcic, Federico Martin
GENOTYPE 1A
HCV
HIV
PEGYLATED INTERFERON
RIBAVIRIN
title_short Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
title_full Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
title_fullStr Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
title_full_unstemmed Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
title_sort Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients
dc.creator.none.fl_str_mv Bolcic, Federico Martin
Laufer, Natalia Lorna
Torres, Carolina
Cassino, Lucila
Reynoso, Rita Paola
Quarleri, Jorge Fabian
author Bolcic, Federico Martin
author_facet Bolcic, Federico Martin
Laufer, Natalia Lorna
Torres, Carolina
Cassino, Lucila
Reynoso, Rita Paola
Quarleri, Jorge Fabian
author_role author
author2 Laufer, Natalia Lorna
Torres, Carolina
Cassino, Lucila
Reynoso, Rita Paola
Quarleri, Jorge Fabian
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv GENOTYPE 1A
HCV
HIV
PEGYLATED INTERFERON
RIBAVIRIN
topic GENOTYPE 1A
HCV
HIV
PEGYLATED INTERFERON
RIBAVIRIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: The rate of non-response to pegylated interferon plus ribavirin (peg-IFN. +. RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5' untranslated (5'UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5'UTR may influence the viral lymphotropism. Methods: We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN. +. RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN. +. RBV non-responders and infected with HCV 1a. Results: Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p<0.001). The number of amino acid variations (mean ± SD) at the NS5A-ISDR domain was higher among HCV/HIV patients than HCV-monoinfected ones (1.80 ± 0.77 vs. 0.95 ± 1.05; p=0.009) but such difference was slightly lower when comparing NS5A-PKRBD sequences (2.47 ± 1.13 vs. 1.60 ± 1.57; p=0.06). No differences were found at the E2-PePHD (0 ± 0 vs. 0.2 ± 0.4). At intra-HIV coinfected patient level, only minor (HCV genetic analysis) or no (HCV substitution rate and quasispecies heterogeneity) changes were observed during therapy (basal, 24. h, 4. weeks, and 12. weeks). Conclusions: Among HCV-1a/HIV coinfected and HCV-monoinfected peg-IFN. +. RBV non-responder patients, the HCV variability at the 5'UTR, E2-PePHD and NS5A-PKRBD/ISDR domains was mostly comparable exhibiting a low number of variations. Four well-defined amino acid substitutions in NS5A-ISDR domain appeared most frequently when HIV coexists. The interferon-based therapy did not exert any effect in the variation, selection or diversity in the above mentioned HCV regions that could influence clinical responsiveness to IFN therapy.
Fil: Bolcic, Federico Martin. 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
Fil: Laufer, Natalia Lorna. 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
Fil: Torres, Carolina. 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. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Cassino, Lucila. 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
Fil: Reynoso, Rita Paola. 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
Fil: Quarleri, Jorge Fabian. 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 Background: The rate of non-response to pegylated interferon plus ribavirin (peg-IFN. +. RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5' untranslated (5'UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5'UTR may influence the viral lymphotropism. Methods: We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN. +. RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN. +. RBV non-responders and infected with HCV 1a. Results: Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p<0.001). The number of amino acid variations (mean ± SD) at the NS5A-ISDR domain was higher among HCV/HIV patients than HCV-monoinfected ones (1.80 ± 0.77 vs. 0.95 ± 1.05; p=0.009) but such difference was slightly lower when comparing NS5A-PKRBD sequences (2.47 ± 1.13 vs. 1.60 ± 1.57; p=0.06). No differences were found at the E2-PePHD (0 ± 0 vs. 0.2 ± 0.4). At intra-HIV coinfected patient level, only minor (HCV genetic analysis) or no (HCV substitution rate and quasispecies heterogeneity) changes were observed during therapy (basal, 24. h, 4. weeks, and 12. weeks). Conclusions: Among HCV-1a/HIV coinfected and HCV-monoinfected peg-IFN. +. RBV non-responder patients, the HCV variability at the 5'UTR, E2-PePHD and NS5A-PKRBD/ISDR domains was mostly comparable exhibiting a low number of variations. Four well-defined amino acid substitutions in NS5A-ISDR domain appeared most frequently when HIV coexists. The interferon-based therapy did not exert any effect in the variation, selection or diversity in the above mentioned HCV regions that could influence clinical responsiveness to IFN therapy.
publishDate 2012
dc.date.none.fl_str_mv 2012-08
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/11336/198538
Bolcic, Federico Martin; Laufer, Natalia Lorna; Torres, Carolina; Cassino, Lucila; Reynoso, Rita Paola; et al.; Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients; Elsevier Science; Antiviral Research; 95; 2; 8-2012; 72-81
0166-3542
CONICET Digital
CONICET
url http://hdl.handle.net/11336/198538
identifier_str_mv Bolcic, Federico Martin; Laufer, Natalia Lorna; Torres, Carolina; Cassino, Lucila; Reynoso, Rita Paola; et al.; Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients; Elsevier Science; Antiviral Research; 95; 2; 8-2012; 72-81
0166-3542
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2012.05.015
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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
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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