Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes
The ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute...
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MDPI AG
2021-05-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/6/1193 |
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| author | Anshika Sharma Joe W. Ong Mun Fai Loke Eng Guan Chua Joseph J. Lee Hyung Won Choi Yee Joo Tan Sunil K. Lal Vincent T. Chow |
| author_facet | Anshika Sharma Joe W. Ong Mun Fai Loke Eng Guan Chua Joseph J. Lee Hyung Won Choi Yee Joo Tan Sunil K. Lal Vincent T. Chow |
| author_sort | Anshika Sharma |
| collection | DOAJ |
| description | The ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute and long-term complications of COVID-19. In this study, to better understand the biological roles of critical SARS-CoV-2 proteins, we determined and compared the host transcriptomic responses of the HL-CZ human pro-monocytic cell line upon transfection with key viral genes encoding the spike S1 subunit, S2 subunit, nucleocapsid protein (NP), NSP15 (endoribonuclease), and NSP16 (2′-O-ribose-methyltransferase). RNA sequencing followed by gene set enrichment analysis and other bioinformatics tools revealed that host genes associated with topologically incorrect protein, virus receptor activity, heat shock protein binding, endoplasmic reticulum stress, antigen processing and presentation were up-regulated in the presence of viral spike S1 expression. With spike S2 expression, pro-monocytic genes associated with the interferon-gamma-mediated signaling pathway, regulation of phosphatidylinositol 3-kinase activity, adipocytokine signaling pathway, and insulin signaling pathway were down-regulated, whereas those associated with cytokine-mediated signaling were up-regulated. The expression of NSP15 induced the up-regulation of genes associated with neutrophil degranulation, neutrophil-mediated immunity, oxidative phosphorylation, prion disease, and pathways of neurodegeneration. The expression of NSP16 resulted in the down-regulation of genes associated with S-adenosylmethionine-dependent methyltransferase activity. The expression of NP down-regulated genes associated with positive regulation of neurogenesis, nervous system development, and heart development. Taken together, the complex transcriptomic alterations arising from these viral-host gene interactions offer useful insights into host genes and their pathways that potentially contribute to SARS-CoV-2 pathogenesis. |
| first_indexed | 2024-03-10T10:49:22Z |
| format | Article |
| id | doaj.art-00df3746a6c64815abfddc17963584e0 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T10:49:22Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-00df3746a6c64815abfddc17963584e02023-11-21T22:18:45ZengMDPI AGMicroorganisms2076-26072021-05-0196119310.3390/microorganisms9061193Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 GenesAnshika Sharma0Joe W. Ong1Mun Fai Loke2Eng Guan Chua3Joseph J. Lee4Hyung Won Choi5Yee Joo Tan6Sunil K. Lal7Vincent T. Chow8Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeMarshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA 6009, AustraliaDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, SingaporeInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeSchool of Science, Tropical Medicine and Biology Platform, Monash University Malaysia, Subang Jaya 47500, Selangor, MalaysiaInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeThe ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute and long-term complications of COVID-19. In this study, to better understand the biological roles of critical SARS-CoV-2 proteins, we determined and compared the host transcriptomic responses of the HL-CZ human pro-monocytic cell line upon transfection with key viral genes encoding the spike S1 subunit, S2 subunit, nucleocapsid protein (NP), NSP15 (endoribonuclease), and NSP16 (2′-O-ribose-methyltransferase). RNA sequencing followed by gene set enrichment analysis and other bioinformatics tools revealed that host genes associated with topologically incorrect protein, virus receptor activity, heat shock protein binding, endoplasmic reticulum stress, antigen processing and presentation were up-regulated in the presence of viral spike S1 expression. With spike S2 expression, pro-monocytic genes associated with the interferon-gamma-mediated signaling pathway, regulation of phosphatidylinositol 3-kinase activity, adipocytokine signaling pathway, and insulin signaling pathway were down-regulated, whereas those associated with cytokine-mediated signaling were up-regulated. The expression of NSP15 induced the up-regulation of genes associated with neutrophil degranulation, neutrophil-mediated immunity, oxidative phosphorylation, prion disease, and pathways of neurodegeneration. The expression of NSP16 resulted in the down-regulation of genes associated with S-adenosylmethionine-dependent methyltransferase activity. The expression of NP down-regulated genes associated with positive regulation of neurogenesis, nervous system development, and heart development. Taken together, the complex transcriptomic alterations arising from these viral-host gene interactions offer useful insights into host genes and their pathways that potentially contribute to SARS-CoV-2 pathogenesis.https://www.mdpi.com/2076-2607/9/6/1193SARS-CoV-2RNA-sequencingSpike S1Spike S2Nucleocapsid (NP)endoribonuclease (NSP15) |
| spellingShingle | Anshika Sharma Joe W. Ong Mun Fai Loke Eng Guan Chua Joseph J. Lee Hyung Won Choi Yee Joo Tan Sunil K. Lal Vincent T. Chow Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes Microorganisms SARS-CoV-2 RNA-sequencing Spike S1 Spike S2 Nucleocapsid (NP) endoribonuclease (NSP15) |
| title | Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes |
| title_full | Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes |
| title_fullStr | Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes |
| title_full_unstemmed | Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes |
| title_short | Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes |
| title_sort | comparative transcriptomic and molecular pathway analyses of hl cz human pro monocytic cells expressing sars cov 2 spike s1 s2 np nsp15 and nsp16 genes |
| topic | SARS-CoV-2 RNA-sequencing Spike S1 Spike S2 Nucleocapsid (NP) endoribonuclease (NSP15) |
| url | https://www.mdpi.com/2076-2607/9/6/1193 |
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