HEV ORF3

Hepatitis E virus (HEV) is a small, non-enveloped RNA virus that causes acute viral hepatitis E, a significant public health concern worldwide. The virus has three open reading frames (ORFs), among which the ORF3 protein plays a crucial role in the virus’s life cycle and pathogenesis.

The ORF3 protein of HEV is a multifunctional regulatory protein involved in various aspects of the viral life cycle, including viral replication, modulation of host cell signaling, and immune evasion. It is known to interact with several host proteins, influencing their functions to create an environment conducive to viral replication and release.

1. Regulation of Host Gene Expression: The ORF3 protein modulates the expression of liver-specific genes by affecting the localization of hepatocyte nuclear factor 4 (HNF4). It increases the phosphorylation of HNF4 through the ERK and Akt kinases, impairing its nuclear translocation and downregulating HNF4-responsive genes . This modulation helps create a favorable environment for viral replication.

2. Interaction with Host Proteins: The ORF3 protein interacts with thioredoxin domain-containing protein 5 (TXNDC5) to promote viral particle release. TXNDC5 stabilizes the ORF3 protein in the endoplasmic reticulum, facilitating its role in viral release . Additionally, ORF3 binds to the src homology 3 (SH3) domains of cellular proteins involved in signal transduction, further influencing host cell signaling pathways .

3. Immune Evasion: The ORF3 protein helps the virus evade the host immune response by modulating various signaling pathways and interacting with host proteins that regulate immune functions. This allows the virus to persist in the host and propagate efficiently.

Recombinant ORF3 protein is produced using various expression systems to study its functions and interactions in detail. These recombinant proteins are crucial for understanding the molecular mechanisms of HEV pathogenesis and developing potential therapeutic interventions.