ArticlePLoS pathogens2019
Innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Immunological aspects of naturally occurring model of hepatitis B virus (HBV) infection, hepatitis B, and HBV-associated hepatocellular carcinoma in the American woodchuck Marmota monax.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- [Current status of research on the impairment of natural killer cell function caused by hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Replication and Expression of the Consensus Genome of Hepatitis B Virus Genotype C from the Chinese Population.Viruses · 2023Article
- Review
- Cryo-EM structures of human hepatitis B and woodchuck hepatitis virus small spherical subviral particles.Science advances · 2022Article
- Review
- Identification of antibodies cross-reactive with woodchuck immune cells and activation of virus-specific and global cytotoxic T cell responses by anti-PD-1 and anti-PD-L1 in experimental chronic hepatitis B and persistent occult hepadnaviral infection.Frontiers in microbiology · 2022Article
- Toll-Like Receptor 7 Agonist RG7854 Mediates Therapeutic Efficacy and Seroconversion in Woodchucks With Chronic Hepatitis B.Frontiers in immunology · 2022Article
- Hepatitis B Virus-Specific Cellular Immunity Contributes to the Outcome of Occult Hepatitis B Virus Infection.Frontiers in microbiology · 2022Article
- Innate immunity and HBV persistence.Current opinion in virology · 2021Review
- Characterization and Application of Precore/Core-Related Antigens in Animal Models of Hepatitis B Virus Infection.Hepatology (Baltimore, Md.) · 2021Article
- Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability.Viruses · 2021Review
- Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer.World journal of gastrointestinal oncology · 2021Review
- Agonistic Activation of Cytosolic DNA Sensing Receptors in Woodchuck Hepatocyte Cultures and Liver for Inducing Antiviral Effects.Frontiers in immunology · 2021Article
- Involvement of Innate Immune Receptors in the Resolution of Acute Hepatitis B in Woodchucks.Frontiers in immunology · 2021Article
- Targeting Host Innate and Adaptive Immunity to Achieve the Functional Cure of Chronic Hepatitis B.Vaccines · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis B virus (HBV) infection have not been identified yet. Information on immune response during the early stages of HBV infection in humans is mainly derived from blood samples of patients with acute hepatitis B (AHB), which are usually obtained after the onset of clinical symptoms. Features of intrahepatic immune response in these patients are less studied due to the difficulty of obtaining multiple liver biopsies. Woodchuck hepatitis virus (WHV) infection in woodchucks is a model for HBV infection in humans. In the present study, five adult woodchucks were experimentally infected with WHV and then followed for 18 weeks. Blood and liver tissues were frequently collected for assaying markers of WHV replication and innate and adaptive immune responses. Liver tissues were further analyzed for pathological changes and stained for important immune cell subsets and cytokines. The increase and subsequent decline of viral replication markers in serum and liver, the elicitation of antibodies against viral proteins, and the induction of virus-specific T-cell responses indicated eventual resolution of acute WHV infection in all animals. Intrahepatic innate immune makers stayed unchanged immediately after the infection, but increased markedly during resolution, as determined by changes in transcript levels. The presence of interferon-gamma and expression of natural killer (NK) cell markers suggested that a non-cytolytic response mechanism is involved in the initial viral control in liver. This was followed by the expression of T-cell markers and cytolytic effector molecules, indicating the induction of a cytolytic response mechanism. Parallel increases in regulatory T-cell markers suggested that this cell subset participates in the overall immune cell infiltration in liver and/or has a role in regulating AHB induced by the cytolytic response mechanism. Since the transcript levels of immune cell markers in blood, when detectable, were lower than in liver, and the kinetics, except for NK-cells and interferon-gamma, did not correlate well with their intrahepatic expression, this further indicated enrichment of immune cells within liver. Conclusion: The coordinated interplay of innate and adaptive immunity mediates viral clearance in the woodchuck animal model of HBV infection. The initial presence of NK-cell associated interferon-gamma response points to an important role of this cytokine in HBV resolution.
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