Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice

Wenqiang Ma¹, Shihua Li², Shuoqian Ma¹, Lina Jia¹, Fuchun Zhang³, Yong Zhang¹, Jingyuan Zhang¹, Gary Wong², Shanshan Zhang¹, Xuancheng Lu⁴, Mei Liu⁵, Jinghua Yan², Wei Li⁶, Chuan Qin⁷, Daishu Han⁸, Chengfeng Qin⁹, Na Wang¹, Xiangdong Li¹⁰, George Fu Gao¹¹

Affiliations

¹ State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
² CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
³ Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
⁴ Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
⁵ Department of Pathology, Chinese PLA General Hospital, Beijing 102628, China.
⁶ Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
⁷ 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.
⁸ School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
⁹ Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
¹⁰ State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: xiangdongli@cau.edu.cn.
¹¹ 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.

PMID: 27884405
DOI: 10.1016/j.cell.2016.11.016

Free article

Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice

Wenqiang Ma et al. Cell. 2016.

Free article

. 2016 Dec 1;167(6):1511-1524.e10.

doi: 10.1016/j.cell.2016.11.016. Epub 2016 Nov 21.

Authors

Affiliations

¹ State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
² CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
³ Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
⁴ Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
⁵ Department of Pathology, Chinese PLA General Hospital, Beijing 102628, China.
⁶ Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
⁷ 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.
⁸ School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
⁹ Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
¹⁰ State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: xiangdongli@cau.edu.cn.
¹¹ 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.

PMID: 27884405
DOI: 10.1016/j.cell.2016.11.016

Erratum in

Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.
Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y, Zhang J, Wong G, Zhang S, Lu X, Liu M, Yan J, Li W, Qin C, Han D, Qin C, Wang N, Li X, Gao GF. Ma W, et al. Cell. 2017 Jan 26;168(3):542. doi: 10.1016/j.cell.2017.01.009. Cell. 2017. PMID: 28129543 No abstract available.

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.

Keywords: AXL; Zika virus; male infertility; orchitis-epididymitis.

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Comment in

Re: Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.
Niederberger C. Niederberger C. J Urol. 2017 Aug;198(2):242. doi: 10.1016/j.juro.2017.05.059. Epub 2017 May 16. J Urol. 2017. PMID: 29370627 No abstract available.

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Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice

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Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice

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