title: Zika virus causes testicular atrophy.
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 infectedIfnar1-/-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.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Uraki
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Kellie Ann
authors.initials: KA
authors.lastname: Jurado
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Householder
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Laura J
authors.identifier: 0000-0002-2437-6518
authors.initials: LJ
authors.lastname: Yockey
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Hastings
authors.affiliation: 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.
authors.forename: Robert J
authors.identifier: 0000-0002-2055-5885
authors.initials: RJ
authors.lastname: Homer
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Akiko
authors.identifier: 0000-0002-7824-9856
authors.initials: A
authors.lastname: Iwasaki
authors.affiliation: 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.
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000818:Animals; D001284:Atrophy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000821:virology; D013739:Testosterone / Q000097:blood*; D014779:Virus Replication / Q000502:physiology*; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000097:blood / Q000235:genetics / Q000473:pathology
chemical_list: C508032:Ifnar1 protein, mouse; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta; D013739:Testosterone
keywords: Ifnar1 KO mice; Leydig cell; Testicular atrophy; Testosterone; Zika virus; flavivirus