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| Pàgina inicial > Articles > Articles publicats > Population Disequilibrium as Promoter of Adaptive Explorations in Hepatitis C Virus |
(Centro de Biología Molecular Severo Ochoa) (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz) (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz) (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz) (Centro de Biología Molecular Severo Ochoa) (Centro de Astrobiología (Madrid)) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)| Data: | 2021 |
| Resum: | Replication of RNA viruses is characterized by exploration of sequence space which facilitates their adaptation to changing environments. It is generally accepted that such exploration takes place mainly in response to positive selection, and that further diversification is boosted by modifications of virus population size, particularly bottleneck events. Our recent results with hepatitis C virus (HCV) have shown that the expansion in sequence space of a viral clone continues despite prolonged replication in a stable cell culture environment. Diagnosis of the expansion was based on the quantification of diversity indices, the occurrence of intra-population mutational waves (variations in mutant frequencies), and greater individual residue variations in mutant spectra than those anticipated from sequence alignments in data banks. In the present report, we review our previous results, and show additionally that mutational waves in amplicons from the NS5A-NS5B-coding region are equally prominent during HCV passage in the absence or presence of the mutagenic nucleotide analogues favipiravir or ribavirin. In addition, by extending our previous analysis to amplicons of the NS3- and NS5A-coding region, we provide further evidence of the incongruence between amino acid conservation scores in mutant spectra from infected patients and in the Los Alamos National Laboratory HCV data banks. We hypothesize that these observations have as a common origin a permanent state of HCV population disequilibrium even upon extensive viral replication in the absence of external selective constraints or changes in population size. Such a persistent disequilibrium-revealed by the changing composition of the mutant spectrum-may facilitate finding alternative mutational pathways for HCV antiviral resistance. The possible significance of our model for other genetically variable viruses is discussed. |
| Ajuts: | Ministerio de Economía y Competitividad SAF2014-52400-R Agencia Estatal de Investigación SAF2017-87846-R Ministerio de Economía y Competitividad BFU2017-91384-EXP Instituto de Salud Carlos III PI18/00210 Instituto de Salud Carlos III CPII19/00001 Instituto de Salud Carlos III PI19/00301 Ministerio de Economía y Competitividad IO2016-79618R Agencia Estatal de Investigación PID2019-104903RB-I00 Instituto de Salud Carlos III PFIS FI19/00119 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Viral quasispecies ; Hepatitis C virus ; Mutational waves ; Residue conservation ; Sequence space ; Antiviral drug resistance ; Universal vaccines ; COVID-19 |
| Publicat a: | Viruses, Vol. 13 (april 2021) , ISSN 1999-4915 |
