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(Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Medicina) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Medicina) (Universitat Autònoma de Barcelona. Departament de Medicina) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Departament de Medicina) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Departament de Medicina)
| Date: | 2024 |
| Abstract: | The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies. |
| Grants: | Agencia Estatal de Investigación PID2021-126447OB-I00 Instituto de Salud Carlos III PI19/00301 Instituto de Salud Carlos III PI22/00258 Instituto de Salud Carlos III PI22/00023 Instituto de Salud Carlos III PI23/01065 "la Caixa" Foundation LCF/BQ/DR23/12000020 |
| Rights: | 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.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Enhanced fitness ; Flat-like quasispecies ; Mutagens ; Near-flat ; Regular quasispecies ; Resistance-associated mutations (RAS) ; Viral treatment failures |
| Published in: | Microorganisms, Vol. 12 (may 2024) , ISSN 2076-2607 |
