The Hepatitis E Virus ORF3 Protein Regulates the Expression of Liver-Specific Genes by Modulating Localization of Hepatocyte Nuclear Factor 4
2011

The Hepatitis E Virus ORF3 Protein Regulates Liver-Specific Gene Expression

publication 10 minutes Evidence: moderate

Author Information

Author(s): Chandra Vivek, Holla Prasida, Ghosh Dhrubaa, Chakrabarti Debarshi, Padigaru Muralidhara, Jameel Shahid

Primary Institution: International Centre for Genetic Engineering and Biotechnology

Hypothesis

The ORF3 protein of the hepatitis E virus modulates the localization of hepatocyte nuclear factor 4, affecting liver-specific gene expression.

Conclusion

The study found that the ORF3 protein increases the phosphorylation of HNF4, impairing its nuclear localization and reducing the expression of liver-specific genes.

Supporting Evidence

  • 221 genes were downregulated and 115 genes were upregulated in ORF3-expressing cells.
  • 79 of the downregulated genes were known targets of hepatocyte nuclear factor 4 (HNF4).
  • Phosphorylation of HNF4 was increased in ORF3-expressing cells, leading to impaired nuclear localization.

Takeaway

The hepatitis E virus has a protein that changes how liver genes work, which might help the virus grow better.

Methodology

Huh7 hepatoma cells were infected with recombinant adenoviruses expressing pORF3, and gene expression was analyzed using microarray techniques.

Potential Biases

Two authors are affiliated with a commercial company, which may introduce bias.

Limitations

The study could not directly demonstrate the effects of ORF3 on HEV replication in the Huh7 culture model.

Participant Demographics

Huh7 hepatoma cells were used in the study.

Digital Object Identifier (DOI)

10.1371/journal.pone.0022412

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