Sheng Zi-Yang, Gao Na, Wang Zhao-Yang, Cui Xiao-Yun, Zhou De-Shan, Fan Dong-Ying, Chen Hui, Wang Pei-Gang, An Jing
Department of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityBeijing, China.
Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical UniversityBeijing, China.
Front Cell Infect Microbiol. 2017 Jun 21;7:272. doi: 10.3389/fcimb.2017.00272. eCollection 2017.
Flaviviruses including Dengue virus (DENV), Yellow fever virus (YFV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) are global health problems that caused several serious diseases such as fever, hemorrhagic fever, and encephalitis in the past century. Recently, Zika virus (ZIKV) which spreads from Asia to American and causes millions of infections emerges as a new dangerous member of the genus of . Unlike other well-known flaviviruses, ZIKV can be transmitted sexually and infect testes in murine models. Its impacts on sperm functions, and the exact susceptible cells, however, are not entirely clear. To investigate these issues, we infected interferon α/β and γ receptors deficient AG6 mice with ZIKV and examined the outcomes of infection using an assortment of physiological, histopathological, immunological, and virological techniques. We found that infected mice displayed signs of reproductive system disorder, altered androgen levels in serum, and high viral load in semen and testes. Additionally, histopathological examinations revealed marked atrophy of seminiferous tubules and significant reduction in lumen size. Notably, these were accompanied by positive staining of ZIKV antigens on sertoli cells, detection of viral particles and vacuole changes within cytoplasm of sertoli cells. The susceptibility of sertoli cells to ZIKV was further validated study using cell lines. Importantly, the disruption of tight junctions within testis and altered sperm morphology were also observed in ZIKV infected mice. It is well-known that tight junctions formed by adjacent sertoli cells are major component of blood testis barrier, which plays important roles in maintenance of microenvironment for spermagenesis in testis. Taken together, these results demonstrate that sertoli cells are susceptible to ZIKV infection, which results in the disruption of tight junctions in testis and causes abnormal spermatogenesis in mice. These results also imply that long-term impact of ZIKV infection on human male reproductive system requires close monitoring.
包括登革热病毒（DENV）、黄热病毒（YFV）、西尼罗河病毒（WNV）和日本脑炎病毒（JEV）在内的黄病毒是全球性的健康问题，在过去的一个世纪里引发了多种严重疾病，如发热、出血热和脑炎。最近，从亚洲传播到美洲并导致数百万感染病例的寨卡病毒（ZIKV）成为该属的一个新的危险成员。与其他知名黄病毒不同，ZIKV可通过性传播，并在小鼠模型中感染睾丸。然而，其对精子功能的影响以及确切的易感细胞尚不完全清楚。为了研究这些问题，我们用ZIKV感染了干扰素α/β和γ受体缺陷的AG6小鼠，并使用各种生理学、组织病理学、免疫学和病毒学技术检查了感染结果。我们发现，受感染的小鼠表现出生殖系统紊乱的迹象，血清中雄激素水平改变，精液和睾丸中的病毒载量很高。此外，组织病理学检查显示生精小管明显萎缩，管腔大小显著减小。值得注意的是，这些变化伴随着支持细胞上ZIKV抗原的阳性染色、支持细胞胞质内病毒颗粒的检测和空泡变化。使用细胞系的研究进一步证实了支持细胞对ZIKV的易感性。重要的是，在ZIKV感染的小鼠中还观察到睾丸内紧密连接的破坏和精子形态的改变。众所周知，相邻支持细胞形成的紧密连接是血睾屏障的主要组成部分，在维持睾丸精子发生的微环境中起重要作用。综上所述，这些结果表明支持细胞易受ZIKV感染，这导致睾丸中紧密连接的破坏，并引起小鼠精子发生异常。这些结果还意味着ZIKV感染对人类男性生殖系统的长期影响需要密切监测。
