ArticleHepatology (Baltimore, Md.)2022
Hepatitis E virus infection activates NOD-like receptor family pyrin domain-containing 3 inflammasome antagonizing interferon response but therapeutically targetable.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Role of NLRP3 in the pathogenesis and treatment of gout arthritis.Frontiers in immunology · 2023Pooled it
- Trial
- Extra-Hepatic Manifestations of Hepatitis E Virus (HEV): A Narrative Review on Meningoencephalitis.Life (Basel, Switzerland) · 2026Review
- Experimental hepatitis E virus genotype 1 infection in three types of wild rodents.PLoS pathogens · 2026Article
- NScience China. Life sciences · 2026Article
- The Differential Effects of Immunosuppressants on Hepatitis E Virus Replication and the Triggered Inflammatory Responses in Macrophages.Journal of viral hepatitis · 2026Article
- Macrophage-augmented organoids recapitulate the complex pathophysiology of viral diseases and enable development of multitarget therapeutics.Nature biomedical engineering · 2025Article
- Role of NLRP3 Inflammasomes in Disorders of Children's Digestive Systems: A Narrative Review.Pediatric reports · 2025Review
- Macrophage-augmented intestinal organoids model virus-host interactions in enteric viral diseases and facilitate therapeutic development.Nature communications · 2025Article
- AMPK activation by hepatitis E virus infection inhibits viral replication through attenuation of autophagosomes and promotion of innate immunity.Cellular and molecular life sciences : CMLS · 2025Article
- Enhancing MyD88 oligomerization is one important mechanism by which IBDV VP2 induces inflammatory response.PLoS pathogens · 2025Article
- Screening of Herbs with Potential Modulation of NLRP3 Inflammasomes for Acute Liver Failure: A Study Based on the Herb-Compound-Target Network and the ssGSEA Algorithm.Current topics in medicinal chemistry · 2025Article
- Hepatitis E virus: from innate sensing to adaptive immune responses.Nature reviews. Gastroenterology & hepatology · 2024Review
- Hepatitis B virus-mediated sodium influx contributes to hepatic inflammation via synergism with intrahepatic danger signals.iScience · 2024Article
- Clinical characteristics of 1279 patients with hepatitis E in Tianjin.Epidemiology and infection · 2023Article
- Review
- Hepatitis E virus infection remodels the mature tRNAome in macrophages to orchestrate NLRP3 inflammasome response.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- [Research progress in the etiology of hepatitis type E virus].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Review
- Exploring the potential targets of theFrontiers in veterinary science · 2023Article
- Animal Models for Hepatitis E Virus.Advances in experimental medicine and biology · 2023Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsHEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting. APPROACH AND
resultsWe measured IL-1β secretion, the hallmark of inflammasome activation, in serum of HEV-infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte-derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL-1β production. A profound increase of IL-1β secretion was further observed in HEV-infected patients (1,733 ± 1,234 pg/mL; n = 70) compared to healthy persons (731 ± 701 pg/mL; n = 70). Given that macrophages are the drivers of inflammatory response, we found that inoculation with infectious HEV particles robustly triggered NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF-κB signaling activation as a key upstream event of HEV-induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibits HEV and inflammasome response without cross-interference.
conclusionsHEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting of NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.
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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.