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Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
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.
Insights
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.
Abstract:
EBV and Helicobacter pylori (H. pylori) cause highly prevalent persistent infections as early as in childhood. Both pathogens are associated with gastric carcinogenesis. H. pylori interferes with iron metabolism, enhancing the synthesis of acute-phase proteins hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP), but we do not know whether EBV does the same. In this study, we correlated the EBV antibody levels and the serum levels of hepcidin, CRP, and AGP in 145 children from boarding schools in Mexico City. We found that children IgG positive to EBV antigens (VCA, EBNA1, and EA) presented hepcidin, AGP, and CRP levels higher than uninfected children. Hepcidin and AGP remained high in children solely infected with EBV, while CRP was only significantly high in coinfected children. We observed positive correlations between hepcidin and EBV IgG antibodies (p < 0.5). Using the TCGA gastric cancer database, we also observed an association between EBV and hepcidin upregulation. The TCGA database also allowed us to analyze the two important pathways controlling hepcidin expression, BMP−SMAD and IL-1β/IL-6. We observed only the IL-1β/IL-6-dependent inflammatory pathway being significantly associated with EBV infection. We showed here for the first time an association between EBV and enhanced levels of hepcidin. Further studies should consider EBV when evaluating iron metabolism and anemia, and whether in the long run this is an important mechanism of undernourishment and EBV gastric carcinogenesis.
