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BibTex format

@article{Rothhaar:2025:10.1038/s41467-025-67174-w,
author = {Rothhaar, P and Arand, T and Seong, HG-T and Heuss, C and Tulessin, M and Wang, Z and Förster, C and Schneider, AC and Quistrebert, J and Chai, H and Reineke, M and Benning, L and Honegger, J and Hofmann, M and Thimme, R and Timm, J and STOPHCV, investigators and Schnitzler, P and Merle, U and Shoukry, NH and Bruneau, J and Rodrigo, C and Lloyd, A and Bull, RA and Ansari, MA and Mogler, C and McLauchlan, J and Forns, X and Pérez-Del-Pulgar, S and Lohmann, V},
doi = {10.1038/s41467-025-67174-w},
journal = {Nat Commun},
title = {Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.},
url = {http://dx.doi.org/10.1038/s41467-025-67174-w},
volume = {16},
year = {2025}
}
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TY  - JOUR
AB  - Hepatitis C virus (HCV) exists as a heterogenous quasispecies, but the phenotypic consequences of viral variability are widely unexplored. Here we identify a replication enhancing domain (ReED) in non-structural protein 5A conferring high replication fitness to clinical isolates. Accumulation of mutations in the ReED mediates high genome replication capacity. In a cohort of liver transplant patients, high replicator variants are exclusively found in individuals with severe disease outcome, suggesting that high viral replication fitness is associated with increased viral pathogenesis. Analysis of large sequence cohorts reveals that overall only 10% of viral genomes show genetic signatures of high replicators, which are enriched in recipients of liver transplantations, patients developing hepatocellular carcinoma and in HIV coinfected individuals. Overall, our data suggests that low replication fitness is a hallmark of HCV, contributing to establishment of persistence, whereas high replicators appear to have an advantage under conditions of immune suppression, thereby enforcing pathogenesis.
AU  - Rothhaar,P
AU  - Arand,T
AU  - Seong,HG-T
AU  - Heuss,C
AU  - Tulessin,M
AU  - Wang,Z
AU  - Förster,C
AU  - Schneider,AC
AU  - Quistrebert,J
AU  - Chai,H
AU  - Reineke,M
AU  - Benning,L
AU  - Honegger,J
AU  - Hofmann,M
AU  - Thimme,R
AU  - Timm,J
AU  - STOPHCV,investigators
AU  - Schnitzler,P
AU  - Merle,U
AU  - Shoukry,NH
AU  - Bruneau,J
AU  - Rodrigo,C
AU  - Lloyd,A
AU  - Bull,RA
AU  - Ansari,MA
AU  - Mogler,C
AU  - McLauchlan,J
AU  - Forns,X
AU  - Pérez-Del-Pulgar,S
AU  - Lohmann,V
DO  - 10.1038/s41467-025-67174-w
PY  - 2025///
TI  - Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.
T2  - Nat Commun
UR  - http://dx.doi.org/10.1038/s41467-025-67174-w
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41354652
VL  - 16
ER  -
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