CD8⁺T cell response promotes viral clearance and reduces chances of severe testicular damage in mouse models of long-term Zika virus infection of the testes

Abstract

Zika virus (ZIKV) causes human testicular inflammation and alterations in sperm parameters and causes testicular damage in mouse models. The involvement of individual immune cells in testicular damage is not fully understood. We detected virus in the testes of the interferon (IFN) α/β receptor-/- A129 mice three weeks post-infection and found elevated chemokines in the testes, suggesting chronic inflammation and long-term infection play a role in testicular damage. In the testes, myeloid cells and CD4+ T cells were absent at 7 dpi but were present at 23 days post-infection (dpi), and CD8+ T cell infiltration started at 7 dpi. CD8-/- mice with an antibody-depleted IFN response had a significant reduction in spermatogenesis, indicating that CD8+ T cells are essential to prevent testicular damage during long-term ZIKV infections. Our findings on the dynamics of testicular immune cells and importance of CD8+ T cells functions as a framework to understand mechanisms underlying observed inflammation and sperm alterations in humans.