Wang Qing, Wang Fei, Chen Ran, Liu Weihua, Gao Na, An Jing, Chen Yongmei, Wu Han, Han Daishu
School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Endocrinology. 2021 Dec 1;162(12). doi: 10.1210/endocr/bqab180.
The human testis can be infected by a large number of RNA and DNA viruses. While various RNA virus infections may induce orchitis and impair testicular functions, DNA virus infection rarely affects the testis. Mechanisms underlying the differential effects of RNA and DNA viral infections on the testis remain unclear. In the current study, we therefore examined the effects of viral RNA and DNA sensor signaling pathways on mouse Sertoli cells (SC) and Leydig cells (LC). The local injection of viral RNA analogue polyinosinic-polycytidylic acid [poly(I:C)] into the testis markedly disrupted spermatogenesis, whereas the injection of the herpes simplex virus (HSV) DNA analogue HSV60 did not affect spermatogenesis. Poly(I:C) dramatically induced the expression of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 in SC and LC through Toll-like receptor 3 and interferon β promoter stimulator 1 signaling pathways, impairing the integrity of the blood-testis barrier and testosterone synthesis. Poly(I:C)-induced TNF-α production thus plays a critical role in the impairment of cell functions. In contrast, HSV60 predominantly induced the expression of type 1 interferons and antiviral proteins via the DNA sensor signaling pathway, which did not affect testicular cell functions. Accordingly, the Zika virus induced high levels of TNF-α in SC and LC and impaired their respective cellular functions, whereas Herpes simplex virus type 2 principally induced antiviral responses and did not impair such functions. These results provide insights into the mechanisms by which RNA viral infections impair testicular functions.
人类睾丸可被大量RNA和DNA病毒感染。虽然各种RNA病毒感染可能诱发睾丸炎并损害睾丸功能，但DNA病毒感染很少影响睾丸。RNA和DNA病毒感染对睾丸产生不同影响的潜在机制仍不清楚。因此，在本研究中，我们检测了病毒RNA和DNA传感器信号通路对小鼠支持细胞（SC）和间质细胞（LC）的影响。向睾丸局部注射病毒RNA类似物聚肌苷酸-聚胞苷酸[poly（I:C）]显著破坏精子发生，而注射单纯疱疹病毒（HSV）DNA类似物HSV60对精子发生没有影响。Poly（I:C）通过Toll样受体3和干扰素β启动子刺激因子1信号通路显著诱导SC和LC中促炎细胞因子肿瘤坏死因子α（TNF-α）和白细胞介素6的表达，损害血睾屏障的完整性和睾酮合成。因此，Poly（I:C）诱导的TNF-α产生在细胞功能损害中起关键作用。相比之下，HSV60主要通过DNA传感器信号通路诱导1型干扰素和抗病毒蛋白的表达，这并不影响睾丸细胞功能。因此，寨卡病毒在SC和LC中诱导高水平的TNF-α并损害它们各自的细胞功能，而2型单纯疱疹病毒主要诱导抗病毒反应且不损害这些功能。这些结果为RNA病毒感染损害睾丸功能的机制提供了见解。
