Hepatitis E virus infects human testicular tissue and Sertoli cells

文献类型: 外文期刊

第一作者: Liu, Tianxu

作者: Liu, Tianxu;Zhang, Yun;Luo, Yong;He, Qiyu;Wang, Lin;Liu, Tianxu;Zhang, Yun;Luo, Yong;He, Qiyu;Wang, Lin;Cao, Yalei;Weng, Jiaming;Jin, Zirun;Zhang, Zhe;Cao, Yalei;Weng, Jiaming;Jin, Zirun;Zhang, Zhe;Gao, Songzhan;Yang, Yuzhuo;Jiang, Hui;Zhang, He;Xia, Changyou;Yin, Xin

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关键词: Hepatitis E virus; chronic hepatitis E; extrahepatic replication; human testis; Sertoli cells

期刊名称:EMERGING MICROBES & INFECTIONS ( 影响因子:13.2; 五年影响因子:9.9 )

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年卷期: 2024 年 13 卷 1 期

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收录情况: SCI

摘要: Globally, hepatitis E virus (HEV) infections are prevalent. The finding of high viral loads and persistent viral shedding in ejaculate suggests that HEV replicates within the human male genital tract, but its target organ is unknown and appropriate models are lacking. We aimed to determine the HEV tropism in the human testis and its potential influence on male reproductive health. We conducted an ex vivo culture of human testis explants and in vitro culture of primary human Sertoli cells. Clinically derived HEV genotype 1 (HEV1) and HEV3 virions, as well as rat-derived HEV-C1, were used for inoculation. Transcriptomic analysis was performed on testis tissues collected from tacrolimus-treated rabbits with chronic HEV3 infection. Our findings reveal that HEV3, but not HEV1 or HEV-C1, can replicate in human testis explants and primary human Sertoli cells. Tacrolimus treatment significantly enhanced the replication efficiency of HEV3 in testis explants and enabled successful HEV1 infection in Sertoli cells. HEV3 infection disrupted the secretion of several soluble factors and altered the cytokine microenvironment within primary human Sertoli cells. Finally, intratesticular transcriptomic analysis of immunocompromised rabbits with chronic HEV infection indicated downregulation of genes associated with spermatogenesis. HEV can infect the human testicular tissues and Sertoli cells, with increased replication efficiency when exposed to tacrolimus treatment. These findings shed light on how HEV may persist in the ejaculate of patients with chronic hepatitis E and provide valuable ex vivo tools for studying countermeasures.

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