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Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin

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Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin

dc.contributor.author	Cuevas Torrijos, José Manuel
dc.contributor.author	Torres Puente, Manoli
dc.contributor.author	Jiménez Hernández, Núria
dc.contributor.author	Bracho Lapiedra, Maria Alma
dc.contributor.author	García Robles, Inmaculada
dc.contributor.author	Wróbel, Borys
dc.contributor.author	Carnicer, Fernando
dc.contributor.author	Olmo, Juan del
dc.contributor.author	Ortega González, Enrique
dc.contributor.author	Moya, Andrés
dc.contributor.author	González Candelas, Fernando
dc.date.accessioned	2010-07-13T08:01:03Z
dc.date.available	2010-07-13T08:01:03Z
dc.date.issued	2008
dc.identifier.citation	Cuevas, JM; Torres-Puente, M; Jiménez-Hernández, N; Bracho, MA; García-Robles, I; Wrobel, B; Carnicer, F; del Olmo, J; Ortega, E; Moya, A; González-Candelas, F. Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin. En PLoS One. 2008 Aug 26;3(8):e3058.	en
dc.identifier.uri	http://hdl.handle.net/10550/15986
dc.description.abstract	We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective pressures.	en
dc.language.iso	en	en
dc.subject	Hepatitis C virus; Genetic variability; Interferon; Ribavirin; Combined therapy	en
dc.title	Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin	en
dc.type	journal article	es_ES
dc.subject.unesco	UNESCO::CIENCIAS DE LA VIDA::Genética ::Otras	en
dc.identifier.doi	10.1371/journal.pone.0003058	en
dc.type.hasVersion	VoR	es_ES
dc.identifier.url	http://ukpmc.ac.uk/ptpmcrender.cgi?aid=1635067&blobtype=pdf	en