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Epstein-Barr Virus Infection Is Associated with Elevated Hepcidin Levels
Ximena Duque1, Eugenia Mendoza1, Segundo Morán2
1Infectious Diseases Research Unit, Mexican Institute of Social Security, Mexico City 06725, Mexico.
International Journal of Molecular Sciences
|January 21, 2023
Summary
Epstein-Barr virus (EBV) infection in children is linked to higher levels of hepcidin, a protein affecting iron metabolism. This suggests EBV may impact iron levels and contribute to health issues like anemia and gastric cancer.
Area of Science:
- Infectious Diseases
- Immunology
- Gastroenterology
Background:
- Epstein-Barr virus (EBV) and Helicobacter pylori (H. pylori) are common childhood infections linked to gastric cancer.
- H. pylori is known to affect iron metabolism by increasing acute-phase proteins like hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP).
- The impact of EBV on these iron-related proteins is not well understood.
Purpose of the Study:
- To investigate the association between EBV infection and serum levels of hepcidin, CRP, and AGP in children.
- To explore the relationship between EBV and hepcidin regulation pathways in gastric cancer using TCGA data.
Main Methods:
- Serum samples from 145 children in Mexico City were analyzed for EBV antibodies and levels of hepcidin, CRP, and AGP.
- Statistical correlations were performed between EBV seropositivity and protein levels.
- The TCGA gastric cancer database was used to analyze EBV association with hepcidin upregulation and its regulatory pathways (BMP−SMAD and IL-1β/IL-6).
Main Results:
- Children with IgG antibodies to EBV antigens showed significantly higher levels of hepcidin, AGP, and CRP compared to uninfected children.
- Elevated hepcidin and AGP levels were observed in children with sole EBV infection.
- CRP levels were significantly higher only in children coinfected with EBV and H. pylori.
- A positive correlation was found between hepcidin and EBV IgG antibody levels.
- TCGA data analysis revealed an association between EBV and hepcidin upregulation, primarily through the IL-1β/IL-6 inflammatory pathway.
Conclusions:
- This study demonstrates a novel association between EBV infection and increased hepcidin levels in children.
- EBV may influence iron metabolism, potentially contributing to undernourishment and anemia.
- The findings suggest EBV's role in gastric carcinogenesis may be partly mediated by hepcidin dysregulation.
- Further research is warranted to explore EBV's impact on iron metabolism and its long-term health consequences.

