Mungin James W, Chen Xin, Liu Bindong
Centers for AIDS Health Disparity Research, Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA.
Pathogens. 2022 Jul 29;11(8):853. doi: 10.3390/pathogens11080853.
Zika virus (ZIKV) is an emerging flavivirus that causes congenital birth defects and neurological compilations in the human host. Although ZIKV is primarily transmitted through infected mosquitos, recent studies reveal sexual contact as a potential transmission route. In vagina-bearing individuals, the vaginal epithelium constitutes the first line of defense against viruses. However, it is unclear how ZIKV interacts with the vaginal epithelium to initiate ZIKV transmission. In this study, we demonstrate that exposing ZIKV to human vaginal epithelial cells (hVECs) resulted in de novo viral RNA replication, increased envelope viral protein production, and a steady, extracellular release of infectious viral particles. Interestingly, our data show that, despite an increase in viral load, the hVECs did not exhibit significant cytopathology in culture as other cell types typically do. Furthermore, our data reveal that the innate antiviral state of hVECs plays a crucial role in preventing viral cytopathology. For the first time, our data show that interferon epsilon inhibits ZIKV replication. Collectively, our results in this study provide a novel perspective on the viral susceptibility and replication dynamics during ZIKV infection in the human vaginal epithelium. These findings will be instrumental towards developing therapeutic agents aimed at eliminating the pathology caused by the virus.
寨卡病毒（ZIKV）是一种新出现的黄病毒，可在人类宿主中导致先天性出生缺陷和神经并发症。虽然寨卡病毒主要通过受感染的蚊子传播，但最近的研究表明性接触也是一种潜在的传播途径。在有阴道的个体中，阴道上皮构成了抵御病毒的第一道防线。然而，尚不清楚寨卡病毒如何与阴道上皮相互作用以启动寨卡病毒传播。在本研究中，我们证明将寨卡病毒暴露于人类阴道上皮细胞（hVECs）会导致病毒RNA从头复制、包膜病毒蛋白产生增加以及传染性病毒颗粒持续的细胞外释放。有趣的是，我们的数据表明，尽管病毒载量增加，但与其他细胞类型通常的情况不同，hVECs在培养中并未表现出明显的细胞病变。此外，我们的数据显示hVECs的先天性抗病毒状态在预防病毒细胞病变中起关键作用。我们的数据首次表明，干扰素ε可抑制寨卡病毒复制。总体而言，我们在本研究中的结果为人类阴道上皮中寨卡病毒感染期间的病毒易感性和复制动态提供了新的视角。这些发现将有助于开发旨在消除该病毒所致病理的治疗药物。
