Testosterone Protects Mice Against Zika Virus Infection And Suppresses The Inflammatory Response In Brain

Abstract Background: Testosterone is an important hormone affecting human growth and development. Recent studies have shown that testosterone is related to immune regulation. Infection with Zika virus (ZIKV) can cause testicular damage and decrease testosterone secretion. However, whether testosterone plays a function in the pathogenesis of ZIKV is still unclear. The main objective of this study was to understand the role of testosterone in central nervous system injury and inflammation induced by ZIKV. Methods: In this work, a mouse model was used to evaluate the role of testosterone in ZIKV infection. Histopathological analysis, flow cytometry, and real-time PCR were performed to investigate the mechanism by which testosterone improved survival in mice after ZIKV infection.Results: ZIKV infection caused testicular damage and decreased testosterone secretion in mice, and testosterone supplementation after ZIKV infection reduced mortality and pathological symptoms in mice. Histopathological analysis showed that testosterone treatment after ZIKV infection could reduce inflammatory cell infiltration in the brain and alleviate brain injury. Flow cytometry and quantitative real-time PCR results confirmed that testosterone treatment could reduce the CD8+ T cell infiltration and the expression of interferon gamma and inflammatory cytokines induced by ZIKV. Conclusion: Testosterone plays an important protective role in mice during ZIKV infection and can be used as a potential therapeutic treatment for ZIKV infection.