PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan; Department of Statistics, Faculty of Science and Technology, Universitas PGRI Adi Buana, Surabaya, East Java 60234, Indonesia.
Peking University Shenzhen Hospital Cardiovascular Surgery and Department of Cardiac Vascular Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People's Republic of China.
J Infect Public Health. 2024 Jan;17(1):60-69. doi: 10.1016/j.jiph.2023.10.035. Epub 2023 Nov 2.
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.
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.
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.
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.
最近在非流行地区重新出现猴痘（mpox）疫情，引发了对潜在全球爆发的担忧。猴痘病毒（MPV）是一种属于正痘病毒属（痘病毒科）的天花样病毒。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相关信号通路，但 MPV 是否调节其他免疫相关途径尚不清楚。
本研究使用两种不同的时间模式来建立猴痘感染的人永生化上皮癌细胞系（HeLa）。选择这两个孵育 2 小时和 12 小时的时间来确定受 MPV 感染影响的核心调控基因和途径。
使用基因本体论框架、京都基因与基因组百科全书数据库和 MetaCore 软件获得了有价值的见解。具体来说，在感染 MPV 2 小时和 12 小时的 HeLa 细胞中发现了各种途径被富集。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聚类和途径与 2 小时感染组显著相关。这种关联是基于 HSPG2、RHPN2、MYL1、ASPHD2、CA9、VIPR1、SNX12、MGC2752、SLC25A1、PEX19 和 AREG 等基因的调控而确定的。此外，与免疫和细胞运动相关的聚类和途径与 12 小时感染组相关。这种关联是基于 C1orf21、C19orf48、HRK、IL8、GULP1、SCAND2、ATP5C1、FEZ1、SGSH、TACC2、CYP4X1、MMP1、CPB1、P2RY13、WDR27、PRPF4 和 ENDOD1 等基因的调控而确定的。
本研究可以提高我们对猴痘发病机制和感染后后遗症的病理生理学的理解。我们的发现为 MPV 感染的各种模式提供了有价值的见解。
