ABSTRACT
AIM: To assess the effects of hepatitis E virus (HEV) on the production of typeâI interferons (IFNs) and determine the underlying mechanisms. METHODS: We measured the production of interferon (IFN)-alpha and -beta (-α/ß) in genotype 3 HEV-infected C3A cells at different time points (0, 8, 12, 24, 48, 72 and 120 h) by enzyme-linked immunosorbent assay (ELISA). The expression levels of IFN-stimulated gene (ISG)15 in HEV-infected C3A cells at different time points were tested by western blotting. The plasmid-expressing open reading frame 3 (ORF3) or control plasmids (green fluorescent protein-expressing) were transfected into C3A cells, and the levels of IFN-α/ß and ISG15 were evaluated, respectively. Furthermore, the plasmid-expressing ISG15 or small interfering RNA-inhibiting ISG15 was transfected into infected C3A cells. Then, the production of IFN-α/ß was also measured by ELISA. RESULTS: We showed that genotype 3 HEV could enhance the production of IFN-α/ß and induce elevation of ISG15 in C3A cells. HEV ORF3 protein could enhance the production of IFN-α/ß and the expression of ISG15. Additionally, ISG15 silencing enhanced the production of IFN-α/ß. Overexpression of ISG15 resulted in the reduction of IFN-α/ß. CONCLUSION: HEV may promote production of IFN-α/ß and expression of ISG15 via ORF3 in the early stages, and increased ISG15 subsequently inhibited the production of IFN-α/ß.
