{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:56:46Z","timestamp":1784037406085,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National University Health System, National University of Singapore","award":["NUHSRO\/2020\/033"],"award-info":[{"award-number":["NUHSRO\/2020\/033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>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\u2032-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.<\/jats:p>","DOI":"10.3390\/microorganisms9061193","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T21:42:06Z","timestamp":1622497326000},"page":"1193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"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"],"prefix":"10.3390","volume":"9","author":[{"given":"Anshika","family":"Sharma","sequence":"first","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"},{"name":"School of Science, Tropical Medicine and Biology Platform, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe W.","family":"Ong","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-5313","authenticated-orcid":false,"given":"Mun Fai","family":"Loke","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng Guan","family":"Chua","sequence":"additional","affiliation":[{"name":"Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4983-4714","authenticated-orcid":false,"given":"Joseph J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-3088","authenticated-orcid":false,"given":"Hyung Won","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-4497","authenticated-orcid":false,"given":"Yee Joo","family":"Tan","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3548-4853","authenticated-orcid":false,"given":"Sunil K.","family":"Lal","sequence":"additional","affiliation":[{"name":"School of Science, Tropical Medicine and Biology Platform, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-6213","authenticated-orcid":false,"given":"Vincent T.","family":"Chow","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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