ArticleProceedings of the National Academy of Sciences of the United States of America2022
Hepatitis E virus infects brain microvascular endothelial cells, crosses the blood-brain barrier, and invades the central nervous system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Closer Association of Liver Stiffness Than Liver Fat Content With Imaging-Derived Neurovascular Coupling in a Metabolic Dysfunction-Associated Steatotic Liver Disease Cohort.Diabetes, obesity & metabolism · 2026Article
- Extra-Hepatic Manifestations of Hepatitis E Virus (HEV): A Narrative Review on Meningoencephalitis.Life (Basel, Switzerland) · 2026Review
- The evolution of in vitro culture systems for the study of hepatitis E virus infection.Virology · 2026Review
- Neurovascular Contacts in the Pathophysiology of Neuralgic Amyotrophy: An Observational Study.Annals of clinical and translational neurology · 2026Article
- Investigating hepatitis E virus seroprevalence in patients with Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- Hepatitis E virus-associated neurological injury and neurotropic cellular mechanisms.Frontiers in cellular and infection microbiology · 2026Review
- Prevalence, Risk Factors, and Genetic Evolution of Rat Hepatitis E Virus in Small Mammals from Southwestern Yunnan, China.Biology · 2025Article
- Differential miRNA signatures in Hepatitis E Virus Infection: Insights into acute, chronic, and pregnancy-related outcomes.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Review
- Occupational zoonoses, neurological diseases, and public health: A one health approach.Infectious medicine · 2025Article
- Antiviral resistance and barrier integrity at the maternal-fetal interface restrict hepatitis E virus from crossing the placental barrier.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Identification of novel rodent and shrew orthohepeviruses sheds light on hepatitis E virus evolution.Zoological research · 2025Article
- Hepatitis E virus infects human testicular tissue and Sertoli cells.Emerging microbes & infections · 2024Article
- Modeling extrahepatic hepatitis E virus infection in induced human primary neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hepatitis E virus immunosuppressed animal models.BMC infectious diseases · 2024Review
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- Hepatitis E Virus: What More Do We Need to Know?Medicina (Kaunas, Lithuania) · 2024Review
- Relevance of Tacrolimus Trough Concentration and Hepatitis E virus Genetic Changes in Kidney Transplant Recipients With Chronic Hepatitis E.Kidney international reports · 2024Article
- The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders.Antioxidants (Basel, Switzerland) · 2024Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and chronic viral hepatitis. A proportion of HEV-infected individuals also developed neurological diseases such as Guillain-Barré syndrome, neuralgic amyotrophy, encephalitis, and myelitis, although the mechanism remains unknown. In this study, by using an in vitro blood-brain barrier (BBB) model, we first investigated whether HEV can cross the BBB and whether the quasi-enveloped HEV virions are more permissible to the BBB than the nonenveloped virions. We found that both quasi-enveloped and nonenveloped HEVs can similarly cross the BBB and that addition of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has no significant effect on the ability of HEV to cross the BBB in vitro. To explore the possible mechanism of HEV entry across the BBB, we tested the susceptibility of human brain microvascular endothelial cells lining the BBB to HEV infection and showed that brain microvascular endothelial cells support productive HEV infection. To further confirm the in vitro observation, we conducted an experimental HEV infection study in pigs and showed that both quasi-enveloped and nonenveloped HEVs invade the central nervous system (CNS) in pigs, as HEV RNA was detected in the brain and spinal cord of infected pigs. The HEV-infected pigs with detectable viral RNA in CNS tissues had histological lesions in brain and spinal cord and significantly higher levels of proinflammatory cytokines TNF-α and interleukin 18 than the HEV-infected pigs without detectable viral RNA in CNS tissues. The findings suggest a potential mechanism of HEV-associated neuroinvasion.
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