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Updated: Jun 17, 2026
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
Zika virus causes testicular atrophy
Ryuta Uraki1, Jesse Hwang1, Kellie Ann Jurado2
1Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Abstract:
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1 mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males.
Insights
Zika virus (ZIKV) can persist in male mice testes, leading to testicular atrophy and reduced testosterone. This study highlights potential long-term reproductive issues and non-vector-borne transmission risks in males.
Area of Science:
- Virology
- Immunology
- Reproductive Biology
Background:
- Zika virus (ZIKV) is an emerging flavivirus causing fetal abnormalities.
- ZIKV is known to persist in human semen post-infection.
- The impact of ZIKV persistence on male reproductive health requires further investigation.
Purpose of the Study:
- To investigate the consequences of ZIKV persistence in male reproductive organs.
- To determine the effects of ZIKV infection on testicular function and testosterone levels.
Main Methods:
- Infection of Ifnar1 mice with a pathogenic ZIKV strain.
- Monitoring viral replication in blood and testes.
- Assessing viral presence in the epididymis and sperm.
- Measuring testicular size and serum testosterone levels.
Main Results:
- ZIKV replicated persistently in testes, particularly in Leydig cells, even after blood clearance.
- High viral loads were detected in the epididymal lumen and epithelial cells.
- Significant testicular atrophy was observed in infected mice by 21 days post-infection.
- ZIKV infection led to a reduction in serum testosterone levels.
Conclusions:
- ZIKV persistence in testes can cause progressive testicular atrophy and reduced testosterone.
- These findings suggest potential impairment of male fertility following ZIKV infection.
- The study underscores implications for non-vector-borne transmission and long-term reproductive deficiencies in males.
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