A mouse model of Zika virus sexual transmission reveals a limited transmission window shorter than viral RNA persistence in semen

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Abstract
Sexual transmission of Zika virus (ZIKV) presents a distinct public health challenge, yet its kinetics and mechanisms remain poorly defined due to the lack of suitable immunocompetent animal models. Here, we established a mouse model of ZIKV sexual transmission using human STAT2 knock-in (hSTAT2 KI) mice. We show that infected males efficiently transmit ZIKV to females via mating. Beyond sperm, non-sperm components in semen substantially contributed to transmission. ZIKV sexual transmission was time-dependent, peaking early at 5 days post-infection (dpi) and declining rapidly thereafter, with transmission virtually ceasing by 40 dpi—a short transmission window that did not align with the prolonged presence of ZIKV RNA in sperm, suggesting clearance of infectious virus or rising antibody responses. Both African and Asian ZIKV strains displayed similar transmission capacities, indicating evolutionary conservation of this trait. In females, infection resulted in viremia and viral RNA detection in multiple organs of the reproductive tract, with predominant localization in the vagina, where it triggered localized lipid metabolic disturbances with minimal impact on upper tract tissues. Our model recapitulates key aspects of human ZIKV sexual transmission, offering a robust platform for mechanistic study and intervention development.
Funding Information
  • National Natural Science Foundation of China (82372251)
  • National Natural Science Foundation of China (82402618)

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