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Sci Adv. 2017 Feb 22;3(2):e1602899. doi: 10.1126/sciadv.1602899. eCollection 2017 Feb.

Zika virus causes testicular atrophy.

Author information

1
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.; U.S. Department of Veterans Affairs Connecticut Healthcare System Pathology and Laboratory Medicine Service, West Haven, CT 06516, USA.
4
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
5
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, 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.

KEYWORDS:

Ifnar1 KO mice; Leydig cell; Testicular atrophy; Testosterone; Zika virus; flavivirus

PMID:
28261663
PMCID:
PMC5321463
DOI:
10.1126/sciadv.1602899
[Indexed for MEDLINE]
Free PMC Article

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