Integrated bioinformatics approaches to investigate alterations in transcriptomic profiles of monkeypox infected human cell line model

Gangga Anuraga; Jilu Lang; Do Thi Minh Xuan; Hoang Dang Khoa Ta; Jia-Zhen Jiang; Zhengda Sun; Sanskriti Dey; Sachin Kumar; Ayushi Singh; Gagan Kajla; Wei-Jan Wang; Chih-Yang Wang

doi:10.1016/j.jiph.2023.10.035

Integrated bioinformatics approaches to investigate alterations in transcriptomic profiles of monkeypox infected human cell line model

J Infect Public Health. 2024 Jan;17(1):60-69. doi: 10.1016/j.jiph.2023.10.035. Epub 2023 Nov 2.

Authors

Gangga Anuraga¹, Jilu Lang², Do Thi Minh Xuan³, Hoang Dang Khoa Ta⁴, Jia-Zhen Jiang⁵, Zhengda Sun⁶, Sanskriti Dey³, Sachin Kumar⁷, Ayushi Singh⁸, Gagan Kajla⁷, Wei-Jan Wang⁹, Chih-Yang Wang¹⁰

Affiliations

¹ 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.
² 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.
³ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
⁴ PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
⁵ Emergency Department, Huashan Hospital North, Fudan University, Shanghai 201508, People's Republic of China.
⁶ Kaiser Permanente, Northern California Regional Laboratories, The Permanente Medical Group, 1725 Eastshore Hwy, Berkeley, CA 94710, USA.
⁷ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Faculty of Biotechnology and Applied Sciences, Shoolini University of Biotechnology and Management Sciences, Himachal Pradesh, India.
⁸ Faculty of Biotechnology and Applied Sciences, Shoolini University of Biotechnology and Management Sciences, Himachal Pradesh, India.
⁹ Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Cancer Biology and Precision Therapeutics Center and Research Center for Cancer Biology, China Medical University, Taichung, Taiwan. Electronic address: cvcsky@cmu.edu.tw.
¹⁰ 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; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: chihyang@tmu.edu.tw.

PMID: 37992435
DOI: 10.1016/j.jiph.2023.10.035

Abstract

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.

Keywords: Bioinformatics; Cell movement; Cellular metabolism; Immune response; Monkeypox (mpox); Viral replication.

MeSH terms

Adaptor Proteins, Signal Transducing
Computational Biology
Gene Expression Profiling
HeLa Cells
Humans
Mpox (monkeypox)*
Phosphatidylinositol 3-Kinases

Substances

Phosphatidylinositol 3-Kinases
GULP1 protein, human
Adaptor Proteins, Signal Transducing