背景:最近在非流行地区再次出现猴痘(水痘)流行,这引起了人们对潜在全球爆发的担忧。痘病毒(MPV)是一种天花样病毒,属于正痘病毒属(家族:Poxviridae)。尽管研究表明MPV感染抑制了Toll样受体-3和肿瘤坏死因子-α相关的信号通路,MPV是否调节其他免疫相关途径尚不清楚.
方法:在本研究中,两种不同的时间模式用于建立MPV感染的人永生上皮癌细胞系(HeLa)。选择孵育的这两个持续时间2和12小时以鉴定受MPV感染影响的共调节的基因和途径。
结果:使用基因本体框架,京都基因百科全书和基因组数据库,和MetaCore软件产生了有价值的见解。具体来说,发现各种途径在感染MPV2和12小时的HeLa细胞中富集。这些途径包括Notch,CD40,CD95,缺氧诱导因子-1-α,白细胞介素(IL)-1,IL-6,磷酸肌醇3-激酶,核因子-κB,丝裂原活化蛋白激酶,和氧化应激诱导的信号通路。代谢和病毒复制周期的簇和途径与2小时感染组显著相关。基于诸如HSPG2、RHPN2、MYL1、ASPHD2、CA9、VIPR1、SNX12、MGC2752、SLC25A1、PEX19和AREG的基因的调节来鉴定这种关联。此外,发现与免疫和细胞运动相关的簇和途径与12小时感染组相关.这种关联是基于基因如C1orf21,C19orf48,HRK,IL8,GULP1,SCAND2,ATP5C1,FEZ1,SGSH,TACC2、CYP4X1、MMP1、CPB1、P2RY13、WDR27、PRPF4和ENDOD1。
结论:这项研究可以提高我们对水痘的病理生理学和感染后后遗症的潜在机制的理解。我们的发现为MPV感染的各种模式提供了有价值的见解。
BACKGROUND: The recent re-emergence of the monkeypox (mpox) epidemic in nonendemic regions has raised concerns regarding a potential global outbreak. The mpox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus (family: Poxviridae). Although studies suggest that MPV infection suppresses the Toll-like receptor-3- and tumor necrosis factor-α-related signaling pathways, whether MPV regulates other immune-related pathways remains unclear.
METHODS: In this study, two distinct temporal patterns were used for establishing an MPV-infected human immortal epithelial cancer cell line (HeLa). These two durations 2 and 12 h of incubation were selected to identify the coregulated genes and pathways affected by MPV infection.
RESULTS: The use of the Gene Ontology framework, Kyoto Encyclopedia of Genes and Genome database, and MetaCore software yielded valuable insights. Specifically, various pathways were found to be enriched in HeLa cells infected with MPV for 2 and 12 h. These pathways included Notch, CD40, CD95, hypoxia-inducible factor-1-α, interleukin (IL)- 1, IL-6, phosphoinositide 3-kinase, nuclear factor-κB, mitogen-activated protein kinase, and oxidative stress-induced signalling pathways. Clusters and pathways of metabolism and viral replication cycles were significantly associated with the 2-hour infection group. This association was identified based on the regulation of genes such as HSPG2, RHPN2, MYL1, ASPHD2, CA9, VIPR1, SNX12, MGC2752, SLC25A1, PEX19, and AREG. Furthermore, clusters and pathways related to immunity and cell movement were found to be associated with the 12-hour infection group. This association was identified based on the regulation of genes such as C1orf21, C19orf48, HRK, IL8, GULP1, SCAND2, ATP5C1, FEZ1, SGSH, TACC2, CYP4X1, MMP1, CPB1, P2RY13, WDR27, PRPF4, and ENDOD1.
CONCLUSIONS: This study can improve our understanding of the mechanisms underlying the pathophysiology and post-infection sequelae of mpox. Our findings provide valuable insights into the various modes of MPV infection.