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Analysis of institutional authors

Forns, XavierAuthorPerez-Del-Pulgar, SofiaAuthor

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April 2, 2026
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Article

Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease

Publicated to: Nature Communications. 16 (1): 10948- - 2025-12-07 16(1), DOI: 10.1038/s41467-025-67174-w

Authors:

Rothhaar, Paul; Arand, Tomke; Seong, Ha Gyu-Thomas; Heuss, Christian; Tulessin, Margaret; Wang, Zhiqing; Forster, Colin; Schneider, Alina C; Quistrebert, Jocelyn; Chai, Haiting; Reineke, Marvin; Benning, Louise; Honegger, Jonathan; Hofmann, Maike; Thimme, Robert; Timm, Jorg; Schnitzler, Paul; Merle, Uta; Shoukry, Naglaa H; Bruneau, Julie; Rodrigo, Chaturaka; Lloyd, Andrew; Bull, Rowena A; Ansari, M Azim; Mogler, Carolin; McLauchlan, John; Forns, Xavier; Perez-del-Pulgar, Sofia; Lohmann, Volker
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Affiliations

Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ, Canada - Author
German Ctr Infect Res, Partner Site Heidelberg, Heidelberg, Germany - Author
Heidelberg Univ, Dept Infect Dis, Sect Virus Host Interact, Mol Virol, Heidelberg, Germany - Author
Nationwide Childrens Hosp, Abigail Wexner Res Inst, Ctr Vaccines & Immun, Columbus, OH USA - Author
Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH USA - Author
Tech Univ Munich, Inst Pathol, Sch Med & Hlth, Munich, Germany - Author
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS,CIBEREHD, Barcelona, Spain - Author
Univ Duesseldorf, Inst Virol, Fac Med, Dusseldorf, Germany - Author
Univ Freiburg, Freiburg Univ Med Ctr, Fac Med, Dept Med 2, Freiburg, Germany - Author
Univ Glasgow, MRC Univ Glasgow Ctr Virus Res, Coll Med Vet & Life Sci, Glasgow, Scotland - Author
Univ Hosp Heidelberg, Dept Infect Dis Virol, Heidelberg, Germany - Author
Univ Hosp Heidelberg, Dept Internal Med 4, Heidelberg, Germany - Author
Univ Hosp Heidelberg, Dept Nephrol, Heidelberg, Germany - Author
Univ Montreal, Dept Med Familiale, Montreal, PQ, Canada - Author
Univ Montreal, Dept Med, Montreal, PQ, Canada - Author
Univ New South Wales, Fac Med, Sch Biomed Sci, Sydney, NSW, Australia - Author
Univ New South Wales, Kirby Inst, Fac Med, Sydney, NSW, Australia - Author
Univ Oxford, Chinese Acad Med Sci Oxford Inst, Oxford, England - Author
Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England - Author
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Abstract

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.
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Keywords

Carcinoma, hepatocellularCholestatic hepatitisCoinfectionFemaleGenetic variationGenetic-variationGenome, viralGenotype 1bHepacivirusHepatitis cHepatocellular-carcinomaHiv infectionsHumansImmunocompromised hostLiver neoplasmsLiver transplantationLiver-transplantationMaleMutationNs-5 protein, hepatitis c virusPlus ribavirinRibavirin therapyRna replicationRna-dependent rna polymeraseSensitivity-determining regionViral nonstructural proteinsVirological responseVirus replication

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Communications due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 10/136, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences. Notably, the journal is positioned above the 90th percentile.

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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-12:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 2.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 2 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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    Leadership analysis of institutional authors

    This work has been carried out with international collaboration, specifically with researchers from: Australia; Canada; Germany; United Kingdom; United States of America.

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    Awards linked to the item

    Open Access funding enabled and organized by Projekt DEAL.
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