■猪三角洲冠状病毒(PDCoV)是一种全球分布的人畜共患病原体,能够感染猪和人类。为了降低跨物种传播和潜在爆发的风险,表征新的抗病毒基因至关重要,特别是那些来自人类宿主的。
■这项研究使用HIEC-6调查PDCoV感染。用PDCoV感染HIEC-6细胞。在感染后48小时收集样品用于蛋白质组学分析。
■我们在HIEC-6细胞中发现了在PDCoV感染后48小时MRPS6基因的差异表达。基因表达最初增加,但随后下降。进一步探讨MRPS6在PDCoV感染中的作用,我们进行了涉及该基因在HIEC-6和Caco2细胞中的过表达和敲减的实验,分别。我们的发现显示MRPS6的过表达显著抑制PDCoV在HIEC-6细胞中的感染,而在Caco2细胞中敲除MRPS6导致病毒滴度显著增加。此外,我们研究了PDCoV感染与MRPS6表达之间的相关性。随后的研究表明,MRPS6通过干扰素途径激活对IFN-β的产生有增强作用,因此阻碍细胞系统中PDCoV感染的进展。总之,这项研究利用蛋白质组学分析来研究PDCoV感染的HIEC-6细胞中差异蛋白的表达,首次提供了MRPS6基因在PDCoV病毒感染中起限制性作用的证据。
■我们的发现最初验证了MRPS6作为IFN-β途径的上游成分,通过干扰素途径的双重激活促进IRF3,IRF7,STAT1,STAT2和IFN-β产生HIEC-6。
UNASSIGNED: Porcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts.
UNASSIGNED: This research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis.
UNASSIGNED: We discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-β through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection.
UNASSIGNED: Our findings initially provide the validation of MRPS6 as an upstream component of IFN-β pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-β production of HIEC-6 via dual-activation from interferon pathway.