A mutation in the progesterone receptor predisposes to HEV infection in HIV‐positive patients

BACKGROUND AND AIMS: Infection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear. We aimed to study the association between a mutation in the progesterone receptor (PR) named PROGINS and HEV‐infected in HIV‐positive individuals. METHODS: We evaluated the presence of the SNP PROGINS via KASP in serum samples of 64 HIV‐positive individuals and 187 healthy controls. We performed ELISA tests to address the serum levels of IL‐10 and IL‐12, as well as T‐cell stimulation assays in peripheral blood to address immune response in individuals with PROGINS. RESULTS: We found a significant association between the presence of PROGINS mutation and HEV seroprevalence in individuals infected with HIV (30% in HIV+/HEV+ versus 2% in HIV+/HEV, respectively, P = .009). Moreover, we found that HIV+/HEV+ individuals expressing the PROGINS mutation had lower serum levels of IL‐10 and higher levels of IL‐12. The presence of the mutation led to a reduced response upon stimulation of CD4+ and CD8+ T cells compared to those without the mutation, suggesting an immune modulation associated with PROGINS. CONCLUSIONS: Our study identified a mutation in the PR that provides significant insights into mechanisms of HEV infection in immunosuppressed individuals.