Taken together, we proposed a mechanism for the long-term ZIKV infection, in which S100A4+ macrophages not only function as Trojan horses to bring ZIKV into the seminiferous tubules, but also serve as a solid shelter for ZIKV replication even when spermatogenic cells have been largely destroyed by ZIKV infection. This evidence concerns the gene S100A4 and Zika virus infectious disease.