Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients : The Fate of a Quasispecies
Gregori i Font, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ibañez Lligoña, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colomer-Castell, Sergi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Campos, Carolina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Cehic, D (University of Cincinnati)
Quer, Josep 1963- (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2024
Abstract:	Viral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability. As a result, resistant variants may emerge, reducing retreatment effectiveness and increasing the chances of viral relapse. Additionally, using a mutagenic agent in monotherapy can accelerate virus evolution towards a flat-like quasispecies structure. This study examines 19 chronic HCV patients who failed direct-acting antiviral (DAA) treatments, using NGS to analyze quasispecies structure in relation to fibrosis as a marker of infection duration. Results show that HCV evolves towards a flat-like quasispecies structure over time, leading also to advanced liver damage (fibrosis F3 and F4/cirrhosis). Based on our findings and previous research, we propose that the flat-like fitness quasispecies structure is the final stage of any quasispecies in chronic infections unless eradicated. The longer the infection persists, the lower the chances of achieving a cure. Interestingly, this finding may also be applicable to other chronic infection and drug resistance in cancer.
Grants:	Instituto de Salud Carlos III PI22/00258 Ministerio de Educación FPU21/04150 "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:	Quasispecies diversity ; Quasispecies maturity ; Quasispecies fitness ; Fibrosis ; Liver damage ; Antiviral treatment failure
Published in:	Microorganisms, Vol. 12, Núm. 11 (October 2024) , ISSN 2076-2607

DOI: 10.3390/microorganisms12112213
PMID: 39597607

15 p, 1.7 MB

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