Work

Glucose-6-phosphate dehydrogenase deficiency facilitates hepatitis E virus entry and aggravates liver injury

Year: 2025

Type: article

Abstract: BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) is an common enzyme deficiency disease, inducing hemolysis, hyperbilirubinemia, and jaundice, as well as liver dysfunction, in approximately 400 million patients. Patients with G6PDd are more susceptible to viruses infection than those without. However, the incidence and severity of hepatitis E virus (HEV) infection in patients with G6PDd are largely unknown. METHODS: The prevalence of HEV in patients with G6PDd was investigated. Susceptibility to HEV was evaluated in a hepatoma cell line with G6PD knockdown, and the interaction between HEV and G6PD was assessed. RESULTS: The prevalence of HEV infection was higher in patients with G6PDd (23.8%, 25/105) than in patients with normal G6PD levels (0.65%, 2/307), indicating that patients with G6PDd are susceptible to HEV infection. Higher rates of hyperbilirubinemia (64% vs. 36.25%) and pneumonia (28% vs. 12.5%) were observed in HEV-infected patients with G6PDd than in patients with normal G6PD values. G6PD knockdown facilitated HEV entry and aggravated oxidative stress with the significant inhibition of glutathione to benefit viral replication but was restricted by NADPH reduction. Co-IP and colocation assays revealed that HEV ORF3 interacted with G6PD. HEV infection stimulated the expression of G6PD in a manner dependent on nuclear factor E2-related factor 2 activation. Consequently, severe apoptosis was observed in HEV-infected cells with G6PD knockdown. CONCLUSIONS: Patients with G6PDd are susceptible to HEV infection. The facilitation of HEV entry and aggravation of oxidative stress may contribute to HEV susceptibility in patients with G6PDd and severe disease.

Source: Virology Journal

DOI: 10.1186/s12985-025-03031-y