Role of Rab13, Protein Kinase A, and Zonula Occludens-1 in Hepatitis E Virus Entry and Cell-to-Cell Spread: Comparative Analysis of Quasi-Enveloped and Non-Enveloped Forms
2024

Understanding How Hepatitis E Virus Enters Cells and Spreads

publication 10 minutes Evidence: high

Author Information

Author(s): Nagashima Shigeo, Primadharsini Putu Prathiwi, Takahashi Masaharu, Nishiyama Takashi, Murata Kazumoto, Okamoto Hiroaki

Primary Institution: Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine

Hypothesis

The study aims to elucidate the roles of Rab13, protein kinase A, and zonula occludens-1 in the entry mechanisms of both quasi-enveloped and non-enveloped forms of hepatitis E virus.

Conclusion

The study found that both forms of hepatitis E virus rely on Rab13 and protein kinase A for entry, and zonula occludens-1 is crucial for the entry of quasi-enveloped hepatitis E virus and its cell-to-cell spread.

Supporting Evidence

  • The entry of both viral forms is dependent on Rab13 and PKA.
  • Targeted knockdown of zonula occludens-1 significantly impaired the entry of both eHEV and neHEV.
  • In ZO-1 knockout cells, HEV RNA levels did not increase even up to 16 days post-inoculation.
  • Absence of ZO-1 did not affect the adsorption efficiency of eHEV or neHEV.

Takeaway

Hepatitis E virus needs certain proteins to get into cells and spread to other cells, and one of these proteins, called ZO-1, is especially important for the virus with a membrane.

Methodology

The study utilized small interfering RNA (siRNA) and chemical inhibitors to investigate the roles of Rab13, protein kinase A, and tight junction proteins in hepatitis E virus infection.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.3390/pathogens13121130

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