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HERV-K10 as a mediator of immune modulation in hepatitis infections.

Front. Immunol. 16:1624774 (2025)
Publ. Version/Full Text Research data DOI PMC
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The human genome contains ~8% of endogenous retroviruses (HERVs), whose reactivation has been implicated in diseases such as cancer and autoimmune disorders. Among these, HERV-K10 has attracted attention for its potential role in immune modulation and viral infections. This study investigates HERV-K10 expression in hepatitis virus infections, focusing on its impact on host gene expression and immune responses. We analyzed HERV-K10 in PBMCs from patients chronically infected with hepatitis C virus (HCV) and in HBV-infected liver cell models. Our results show a significant upregulation of HERV-K10 in HBV-infected HepG2-NTCP cells, HCV-infected PBMCs, and a trend in HBV-infected primary hepatocytes. HERV-K10 activation was specific to hepatitis infection, as no effect was seen with HBV entry inhibitors, adenovirus 5 infection or infection with other RNA viruses. RNA sequencing of HBV-infected HepG2-NTCP cells revealed distinct clustering based on HERV expression profiles, including HERV-K10 encoding the MAG1 domain, an immune response target. To investigate the potential immunomodulatory role of HERV-K10 MAG1, we vaccinated mice with the MAG1 peptide, which resulted in activation of CD4+ and CD8+ T-cell responses and higher levels of MAG1-specific antibodies. Furthermore, chronic hepatitis B patients exhibited an immune response to MAG1 characterized by elevated levels of Interleukin-6 (IL-6) and interleukin-1β (IL-1β) cytokines. Taken together, our data suggest that HERV-K10 plays an important role in immune modulation during viral hepatitis infection and may contribute to the pathogenesis of autoimmune diseases.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gag1/mag1 ; Herv-k10 ; Hervs ; Autoimmune Diseases ; Hepatitis ; Immune Modulation
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Quellenangaben Volume: 16, Issue: , Pages: , Article Number: 1624774 Supplement: ,
Publisher Frontiers
Reviewing status Peer reviewed
POF-Topic(s) 30203 - Molecular Targets and Therapies
30201 - Metabolic Health
Research field(s) Immune Response and Infection
Genetics and Epidemiology
PSP Element(s) G-502700-009
G-502700-003
G-500600-007
G-502799-701
G-502700-002
G-502700-010
Scopus ID 105017634973
PubMed ID 41041334
Erfassungsdatum 2025-10-08