• HEV infection significantly upregulates ING5 expression in both acute (BALB/c mice) and chronic (rhesus macaques) animal models, as well as in human hepatoma cells (HepG-2).
• This is the first study to demonstrate a direct link between HEV infection and ING5, a tumor suppressor, suggesting a potential mechanism for HEV-associated hepatocarcinogenesis.
• The findings provide novel insights into the pathogenic mechanisms of HEV infection, particularly in immunocompromised patients at risk for chronic hepatitis and HCC.
• The upregulation of ING5 during HEV infection may represent a host defense response or a viral manipulation strategy, warranting further investigation for therapeutic targeting.