TY - JOUR
T1 - Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients :
T2 - The Fate of a Quasispecies
AU - Gregori i Font, Josep
AU - Ibañez Lligoña, Marta
AU - Colomer-Castell, Sergi
AU - Campos, Carolina
AU - Garcia-Cehic, D
AU - Quer, Josep
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/10/31
Y1 - 2024/10/31
N2 - 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.
AB - 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.
KW - Quasispecies diversity
KW - Quasispecies maturity
KW - Quasispecies fitness
KW - Fibrosis
KW - Liver damage
KW - Antiviral treatment failure
KW - antiviral treatment failure
KW - quasispecies maturity
KW - quasispecies diversity
KW - fibrosis
KW - liver damage
KW - quasispecies fitness
UR - http://www.scopus.com/inward/record.url?scp=85210590978&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e7518070-63b7-3963-b901-e3300a576838/
U2 - 10.3390/microorganisms12112213
DO - 10.3390/microorganisms12112213
M3 - Article
C2 - 39597607
SN - 2076-2607
VL - 12
JO - Microorganisms
JF - Microorganisms
IS - 11
M1 - 2213
ER -