Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, Washington, USA.
Sci Rep. 2018 Jun 7;8(1):8702. doi: 10.1038/s41598-018-27027-7.
Confirmed reports of Zika virus (ZIKV) in seminal fluid months after clearance of viremia suggests that ZIKV can establish persistent infection in the seminiferous tubules, an immune privileged site of the testis. The seminiferous tubule epithelium is mainly composed of Sertoli cells that function to nourish and protect developing germ cells. We recently demonstrated that primary human Sertoli cells (hSeC) were highly susceptible to ZIKV as compared to dengue virus without causing cell death and thus may act as a reservoir for ZIKV in the testes. However, the cellular and immune responses of hSeC to infection with ZIKV or any other virus are not yet characterized. Using genome-wide RNA-seq to compare immunoprofiles of hSeC, we show that the most prominent response to ZIKV at early stage of infection was suppression of cell growth and proliferation functional pathways. Peak virus replication was associated with induction of multiple antiviral defense pathways. Unique ZIKV-associated signatures included dysregulation of germ cell-Sertoli cell junction signaling. This study demonstrates that hSeC are capable of signaling through canonical pro-inflammatory pathways and provides insights into unique cell-type-specific response induced by ZIKV in association with viral persistence in the testes.
经证实，寨卡病毒（ZIKV）在血液病毒清除数月后存在于精液中，表明 ZIKV 可在睾丸的生精小管中建立持续感染，这是一个免疫特惠部位。生精小管上皮主要由支持细胞组成，其功能是滋养和保护发育中的精原细胞。我们最近的研究表明，与登革热病毒相比，原代人支持细胞（hSeC）对 ZIKV 高度易感，而不会导致细胞死亡，因此可能是睾丸中 ZIKV 的储库。然而，hSeC 对 ZIKV 或任何其他病毒感染的细胞和免疫反应尚未得到表征。我们使用全基因组 RNA-seq 来比较 hSeC 的免疫图谱，结果表明，在感染早期，hSeC 对 ZIKV 的最主要反应是抑制细胞生长和增殖功能途径。病毒复制高峰与多种抗病毒防御途径的诱导相关。独特的 ZIKV 相关特征包括生殖细胞-支持细胞连接信号转导的失调。这项研究表明，hSeC 能够通过经典的促炎途径发出信号，并深入了解与睾丸中病毒持续存在相关的 ZIKV 诱导的独特细胞类型特异性反应。
