KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry.

IF 4 3区 医学 Q2 VIROLOGY
Jiayuan Sun, Yige Ding, Qian Zhou, Peter Kalds, Jianlin Han, Keshan Zhang, Yinghui Wei, Weiwei Wu, Xiaolong Wang, Wenxin Zheng
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Abstract

The orf virus (ORFV) poses a serious threat to the health of domestic small ruminants (i.e., sheep and goats) and humans on a global scale, causing around $150 million in annual losses to livestock industry. However, the host factors involved in ORFV infection and replication are still elusive. In this study, we compared the RNA-seq profiles of ORFV-infected or non-infected sheep testicular interstitial cells (STICs) and identified a novel host gene, potassium voltage-gated channel subfamily E member 4 (KCNE4), as a key host factor involved in the ORFV infection. Both RNA-seq data and RT-qPCR assay revealed a significant increase in the expression of KCNE4 in the infected STICs from 9 to 48 h post infection (hpi). On the other hand, the RT-qPCR assay detected a decrease in ORFV copy number in both the STICs transfected by KCNE4 siRNA and the KCNE4 knockout (KO) HeLa cells after the ORFV infection, together with a reduced fluorescence ratio of ORFV-GFP in the KO HeLa cells at 24 hpi, indicating KCNE4 to be critical for the ORFV infection. Furthermore, the attachment and internalization assays showed decreased ORFV attachment, internalization, replication, and release by the KO HeLa cells, demonstrating a potential inhibition of ORFV entry into the cells by KCNE4. Pretreatment with the KCNE4 inhibitors such as quinidine and fluoxetine significantly repressed the ORFV infection. All our findings reveal KCNE4 as a novel host regulator of the ORFV entry and replication, shedding new insight into the interactive mechanism of ORFV infection. The study also highlights the K+ channels as possible druggable targets to impede viral infection and disease.

KCNE4 是 Orf 病毒感染的关键宿主因子,可介导病毒进入。
口蹄疫病毒(ORFV)严重威胁着全球家养小反刍动物(即绵羊和山羊)和人类的健康,每年给畜牧业造成约 1.5 亿美元的损失。然而,ORFV感染和复制所涉及的宿主因素仍然难以捉摸。在这项研究中,我们比较了感染或未感染ORFV的绵羊睾丸间质细胞(STICs)的RNA-seq图谱,发现了一个新的宿主基因--钾电压门控通道E亚家族成员4(KCNE4)--是参与ORFV感染的关键宿主因子。RNA-seq数据和RT-qPCR检测均显示,从感染后9到48小时(hpi),KCNE4在受感染STIC中的表达量显著增加。另一方面,RT-qPCR检测发现,在ORFV感染后,KCNE4 siRNA转染的STIC细胞和KCNE4基因敲除(KO)的HeLa细胞中的ORFV拷贝数都有所下降,而且在24 hpi时,KO HeLa细胞中ORFV-GFP的荧光比率也有所降低,这表明KCNE4对ORFV感染至关重要。此外,附着和内化试验显示,KO HeLa细胞对ORFV的附着、内化、复制和释放均有所减少,这表明KCNE4可能抑制了ORFV进入细胞。使用奎尼丁和氟西汀等 KCNE4 抑制剂预处理可显著抑制 ORFV 感染。我们的所有发现揭示了 KCNE4 是 ORFV 进入和复制的新型宿主调控因子,为了解 ORFV 感染的相互作用机制提供了新的视角。这项研究还强调,K+通道可能是阻碍病毒感染和疾病的药物靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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