title: Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.
abstract: Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus infection. Here, we demonstrate that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice. ZIKV induces innate immune responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the production of pro-inflammatory cytokines/chemokines. However, ZIKV does not induce a rapid and abundant cytokine production in peritubular cell and spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and could be the potential repositories for ZIKV. Our study demonstrates a correlation between ZIKV and testis infection/damage and suggests that ZIKV infection, under certain circumstances, can eventually lead to male infertility.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Ma
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Shuoqian
authors.initials: S
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Jia
authors.affiliation: Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
authors.forename: Xuancheng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pathology, Chinese PLA General Hospital, Beijing 102628, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, National Health and Family Planning Commission, Beijing 100021, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: xiangdongli@cau.edu.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: gaof@im.ac.cn.
authors.forename: George Fu
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004822:Epididymis / Q000473:pathology / Q000821:virology; D006801:Humans; D007248:Infertility, Male / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D013737:Testis / Q000473:pathology / Q000821:virology*; D053586:Virus Internalization; D000071244:Zika Virus / Q000302:isolation & purification / Q000502:physiology*; D000071243:Zika Virus Infection / Q000473:pathology / Q000635:transmission / Q000821:virology*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D016207:Cytokines; C508032:Ifnar1 protein, mouse; D011518:Proto-Oncogene Proteins; D053633:Receptor, Interferon alpha-beta; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase
keywords: AXL; Zika virus; male infertility; orchitis-epididymitis