Hepatitis E virus ORF1 encoded non structural protein-host protein interaction network.

Area of Science:

• Virology
• Molecular Biology
• Hepatology

Background:

• Hepatitis E virus (HEV) non-structural polyprotein (nsP) is crucial for viral replication.
• The nsP contains multiple functional domains: Methyltransferase, Y-domain, Protease, X-domain, Helicase, and RNA-dependent RNA polymerase.
• Understanding host-pathogen interactions is key to deciphering viral pathogenesis.

Purpose of the Study:

• To identify human liver cell proteins interacting with HEV ORF1 functional domains.
• To analyze the host-pathogen protein-protein interaction network.
• To elucidate the cellular pathways targeted by HEV during infection.

Main Methods:

• Yeast two-hybrid (Y2H) screening was employed to identify protein-protein interactions.
• Bioinformatic analysis, including comparative interactome analysis, was performed.
• Gene Ontology (GO) enrichment analysis and cellular pathway analysis were conducted.

Main Results:

• 155 protein-protein interactions between HEV ORF1 and human proteins were identified.
• HEV-interacting proteins are central and interconnected within the human interactome.
• Viral proteins preferentially interact with host proteins involved in metabolism, energy generation, immune response, and ubiquitin-proteasomal pathways.

Conclusions:

• HEV ORF1 interacts with key human proteins, suggesting a strategy for viral replication.
• The virus targets host pathways including metabolism, energy generation, immune response, mTOR, and focal adhesion.
• HEV likely exploits host proteins for carbohydrate metabolism, energy generation, and iron homeostasis during infection.