We explored the significance of the expression of hepatitis E virus (HEV) open reading frame 3 (ORF3) in hepatitis E rat models. We also investigated its diagnostic value. Forty Sprague‑Dawley (SD) rats were infected with HEV and 10 uninfected rats were selected for the control group. Rats were sacrificed at 14, 21, 35 and 70 days after infection. They were divided into 4 groups: Model group 1, model group 2, model group 3 and model group 4. ORF3 protein expression level in liver tissue, level of adipokines [fatty acid synthase (FAS), tissue inhibitor of metalloproteinase-2 (TIMP-2) and angio­tensin-converting enzyme inhibitor 2 (ACE-2)], Th1/Th2 cells balance [interferon (IFN), interleukin-4 (IL-4) and Th1/Th2] and the level of immune outcome (levels of CD4+, CD8+ T lymphocytes and CD4+/CD8+) were measured and comp­ared among groups. Our results showed that HEV IgG and HEV RNA levels in the model group 3 were higher than those in the other 3 groups. Compared with the control group, expression level of ORF3 protein in the liver tissue as well as Fas and TIMP levels were significantly higher in the model group 3. ACE-2 level was significantly lower than that of the control group (P<0.05). In the model group 3, IFN-γ, IL-4 and Th1/Th2 levels were meaningfully higher than those of the control group. CD4+ T lymphocytes and CD4+/CD8+ ratio were obviously lower than those in the control group (P<0.05). The expression level of ORF3 was positively correlated with levels of Fas, TIMP-2 and Th1/Th2. It was negatively correlated with ACE-2 and CD4+/CD8+ levels (P<0.05). We concluded that ORF3 expression level was directly related to severity and prognosis, and that ORF3 protein can be considered as a sensitive and specific diagnostic index.

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