ArticleJournal of hepatology2017
High resolution sequencing of hepatitis C virus reveals limited intra-hepatic compartmentalization in end-stage liver disease.
Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Genomic surveillance uncovers regional variation in HCV transmission networks in rural United States.Nature communications · 2025Article
- Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.Journal of hepatology · 2024Article
- Identification of Genetically Related HCV Infections Among Self-Described Injecting Partnerships.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil.Access microbiology · 2022Article
- Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.Virus evolution · 2022Article
- Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma.Life science alliance · 2021Article
- Hepatitis C Virus Transmission Clusters in Public Health and Correctional Settings, Wisconsin, USA, 2016-2017Emerging infectious diseases · 2021Article
- Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.Frontiers in immunology · 2021Article
- Review
- LncRNAs in HCV Infection and HCV-Related Liver Disease.International journal of molecular sciences · 2020Review
- Machine-learning based patient classification using Hepatitis B virus full-length genome quasispecies from Asian and European cohorts.Scientific reports · 2019Article
- Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia.Journal of virology · 2019Article
- The immunology of hepatocellular carcinoma.Nature immunology · 2018Review
- Regulation of the Interferon Response by lncRNAs in HCV Infection.Frontiers in microbiology · 2018Review
- Viral hepatitis and liver cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThe high replication and mutation rate of hepatitis C virus (HCV) results in a heterogeneous population of viral sequences in vivo. HCV replicates in the liver and infected hepatocytes occur as foci surrounded by uninfected cells that may promote compartmentalization of viral variants. Given recent reports showing interferon stimulated gene (ISG) expression in chronic hepatitis C, we hypothesized that local interferon responses may limit HCV replication and evolution.
methodsTo investigate the spatial influence of liver architecture on viral replication we measured HCV RNA and ISG mRNA from each of the 8 Couinaud segments of the liver from 21 patients undergoing liver transplant.
resultsHCV RNA and ISG mRNA levels were comparable across all sites from an individual liver but showed up to 500-fold difference between patients. Importantly, there was no association between ISG and HCV RNA expression across all sites in the liver or plasma. Deep sequencing of HCV RNA isolated from the 8 hepatic sites from two subjects showed a similar distribution of viral quasispecies across the liver and uniform sequence diversity. Single genome amplification of HCV E1E2-envelope clones from 6 selected patients at 2 hepatic sites supported these data and showed no evidence for HCV compartmentalization.
conclusionsWe found no differences between the hepatic and plasma viral quasispecies in all patients sampled. We conclude that in end-stage liver disease HCV RNA levels and the genetic pool of HCV envelope sequences are indistinguishable between distant sites in the liver and plasma, arguing against viral compartmentalization. LAY SUMMARY: HCV is an RNA virus that exists as a quasispecies of closely related genomes that are under continuous selection by host innate and adaptive immune responses and antiviral drug therapy. The primary site of HCV replication is the liver and yet our understanding of the spatial distribution of viral variants within the liver is limited. High resolution sequencing of HCV and monitoring of innate immune responses at multiple sites across the liver identified a uniform pattern of diversity and argues against viral compartmentalization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.