Testosterone protects mice against zika virus infection and suppresses the inflammatory response in the brain

Testosterone is essential to human growth and development as well as immune regulation. Zika virus (ZIKV), an emerging arbovirus associated with neurological complications including neuroinflammation, can also cause testicular damage and decrease testosterone secretion. However, whether the dysregulation of testosterone plays a role in the process of neuroinflammation during ZIKV pathogenesis is still unclear. In this study, we found that ZIKV infection caused testicular damage and decreased testosterone secretion in male mice, and testosterone supplementation after ZIKV infection reduced their mortality and attenuated the pathological symptoms. Further investigation revealed that testosterone treatment after ZIKV infection alleviated inflammation and nerve injury in the mouse brain. Additionally, reduced CD8⁺ T cell infiltration and interferon-gamma production were observed in brains of testosterone-treated mice. Overall, our results demonstrated that testosterone plays a protective role in ZIKV-infected mice, and thus it can be developed as a potential therapeutic drug against ZIKV infection.