{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:47:03Z","timestamp":1761598023283,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T00:00:00Z","timestamp":1543968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001463","name":"Ministry of Defence, Singapore","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001463","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The poxviruses are large, linear, double-stranded DNA viruses about 130 to 230 kbp, that have an animal origin and evolved to infect a wide host range. Variola virus (VARV), the causative agent of smallpox, is a poxvirus that infects only humans, but other poxviruses such as monkey poxvirus and cowpox virus (CPXV) have crossed over from animals to infect humans. Therefore understanding the biology of poxviruses can devise antiviral strategies to prevent these human infections. In this study we used a system-based approach to examine the host responses to three orthopoxviruses, CPXV, vaccinia virus (VACV), and ectromelia virus (ECTV) in the murine macrophage RAW 264.7 cell line. Overall, we observed a significant down-regulation of gene expressions for pro-inflammatory cytokines, chemokines, and related receptors. There were also common and virus-specific changes in the immune-regulated gene expressions for each poxvirus-infected RAW cells. Collectively our results showed that the murine macrophage RAW 264.7 cell line is a suitable cell-based model system to study poxvirus host response.<\/jats:p>","DOI":"10.3390\/v10120692","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T12:22:00Z","timestamp":1544012520000},"page":"692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A System Based-Approach to Examine Cytokine Response in Poxvirus-Infected Macrophages"],"prefix":"10.3390","volume":"10","author":[{"given":"Pui-San","family":"Wong","sequence":"first","affiliation":[{"name":"Defence Medical and Environmental Research Institute, DSO National Labs, Singapore 117510, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Sutejo","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-0750","authenticated-orcid":false,"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sock-Hoon","family":"Ng","sequence":"additional","affiliation":[{"name":"Defence Medical and Environmental Research Institute, DSO National Labs, Singapore 117510, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Sugrue","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4976-7988","authenticated-orcid":false,"given":"Boon-Huan","family":"Tan","sequence":"additional","affiliation":[{"name":"Defence Medical and Environmental Research Institute, DSO National Labs, Singapore 117510, Singapore"},{"name":"Infection and Immunity, LKC School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.virusres.2006.01.016","article-title":"Poxviruses: Past, present and future","volume":"117","author":"Lefkowitz","year":"2006","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.3390\/v7031100","article-title":"The origin of the variola virus","volume":"7","author":"Babkin","year":"2015","journal-title":"Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1002\/jmv.25055","article-title":"Bayesian reconstruction of the evolutionary history and cross-species transition of variola virus and orthopoxviruses","volume":"90","author":"Zehender","year":"2018","journal-title":"J. Med Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15196","DOI":"10.1073\/pnas.0405954101","article-title":"Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox","volume":"101","author":"Jahrling","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1177\/0300985810378649","article-title":"Animal models of orthopoxvirus infection","volume":"47","author":"Chapman","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/978-1-4615-1971-3_57","article-title":"Ectromelia virus establishes a persistent infection in spleen dendritic cells and macrophages of BALB\/c mice following the acute disease","volume":"378","author":"Malicka","year":"1995","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1089\/vim.2016.0173","article-title":"Innate Immune Gene Transcript Level Associated with the Infection of Macrophages with Ectromelia Virus in Two Different Mouse Strains","volume":"30","author":"Dolega","year":"2017","journal-title":"Viral. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hernaez, B., and Alcami, A. (2018). New insights into the immunomodulatory properties of poxvirus cytokine decoy receptors at the cell surface. F1000 Res., 7.","DOI":"10.12688\/f1000research.14238.1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1089\/vim.2013.0003","article-title":"Crosstalk between autophagy and apoptosis in RAW 264.7 macrophages infected with ectromelia orthopoxvirus","volume":"26","author":"Martyniszyn","year":"2013","journal-title":"Viral. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9602","DOI":"10.1128\/JVI.01078-09","article-title":"Inhibition of macrophage activation by the myxoma virus M141 protein (vCD200)","volume":"83","author":"Zhang","year":"2009","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s12272-017-0898-x","article-title":"The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells","volume":"40","author":"Lee","year":"2017","journal-title":"Arch. Pharm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.18632\/oncotarget.14558","article-title":"Comprehensive proteome analysis of lysosomes reveals the diverse function of macrophages in immune responses","volume":"8","author":"Gao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Thiel, N., Keyser, K.A., Lemmermann, N.A., Oduro, J.D., Wagner, K., Elsner, C., Halenius, A., Lenac Rovi\u0161, T., Brinkmann, M.M., and Jonji\u0107, S. (2016). The Mouse Cytomegalovirus Gene m42 Targets Surface Expression of the Protein Tyrosine Phosphatase CD45 in Infected Macrophages. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1006057"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1128\/JVI.07071-11","article-title":"Sensing adenovirus infection: Activation of interferon regulatory factor 3 in RAW 264.7 cells","volume":"86","author":"Stein","year":"2012","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dabrowski, P.W., Radoni\u0107, A., Kurth, A., and Nitsche, A. (2013). Genome-wide comparison of cowpox viruses reveals a new clade related to Variola virus. PLoS ONE., 8.","DOI":"10.1371\/journal.pone.0079953"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Franke, A., Pfaff, F., Jenckel, M., Hoffmann, B., H\u00f6per, D., Antwerpen, M., Meyer, H., Beer, M., and Hoffmann, D. (2017). Classification of Cowpox Viruses into Several Distinct Clades and Identification of a Novel Lineage. Viruses, 9.","DOI":"10.3390\/v9060142"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1373\/clinchem.2006.068635","article-title":"Real-time PCR to identify variola virus or other human pathogenic orthopox viruses","volume":"53","author":"Scaramozzino","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liem, J., and Liu, J. (2016). Stress Beyond Translation: Poxviruses and More. Viruses, 8.","DOI":"10.3390\/v8060169"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1099\/vir.0.055921-0","article-title":"Vaccinia virus immune evasion: Mechanisms, virulence and immunogenicity","volume":"94","author":"Smith","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.imlet.2003.11.015","article-title":"IL-15 induces IFN-beta and iNOS gene expression, and antiviral activity of murine macrophage RAW 264.7 cells","volume":"91","author":"Liu","year":"2004","journal-title":"Immunol. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.chom.2007.08.005","article-title":"Colocalization of transcription and translation within cytoplasmic poxvirus factories coordinates viral expression and subjugates host functions","volume":"2","author":"Katsafanas","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1099\/0022-1317-82-9-2095","article-title":"The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence","volume":"82","author":"Ng","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1099\/vir.0.81417-0","article-title":"Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy","volume":"87","author":"Clark","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1128\/JVI.02111-07","article-title":"An ectromelia virus protein that interacts with chemokines through their glycosaminoglycan binding domain","volume":"82","author":"Smith","year":"2008","journal-title":"J. Virol."},{"key":"ref_25","first-page":"1223","article-title":"Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins","volume":"81","author":"Smith","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1128\/JVI.76.3.1124-1134.2002","article-title":"Inhibition of Interferons by Ectromelia Virus","volume":"76","author":"Smith","year":"2002","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1096\/fj.09-144733","article-title":"The highly virulent variola and monkeypox viruses express secreted inhibitors of type I. interferon","volume":"24","author":"Damon","year":"2010","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1128\/JVI.78.11.5820-5834.2004","article-title":"Microarray analysis reveals characteristic changes of host cell gene expression in response to attenuated modified vaccinia virus Ankara infection of human HeLa cells","volume":"78","author":"Guerra","year":"2004","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6493","DOI":"10.1128\/JVI.77.11.6493-6506.2003","article-title":"Cellular gene expression survey of vaccinia virus infection of human HeLa cells","volume":"77","author":"Guerra","year":"2003","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1128\/JVI.80.2.985-998.2006","article-title":"Host response to the attenuated poxvirus vector NYVAC: Upregulation of apoptotic genes and NF-kappaB-responsive genes in infected HeLa cells","volume":"80","author":"Guerra","year":"2006","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bourquain, D., Dabrowski, P.W., and Nitsche, A. (2013). Comparison of host cell gene expression in cowpox, monkeypox or vaccinia virus-infected cells reveals virus-specific regulation of immune response genes. Virol. J., 10.","DOI":"10.1186\/1743-422X-10-61"},{"key":"ref_32","first-page":"1044","article-title":"Ectromelia virus upregulates the expression of heat shock protein 70 to promote viral replication","volume":"42","author":"Cheng","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8707","DOI":"10.1128\/JVI.00444-07","article-title":"Distinct gene expression profiling after infection of immature human monocyte-derived dendritic cells by the attenuated poxvirus vectors MVA and NYVAC","volume":"81","author":"Guerra","year":"2007","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.1016\/j.vaccine.2008.07.050","article-title":"Gene profiling analysis of ALVAC infected human monocyte derived dendritic cells","volume":"26","author":"Harenberg","year":"2008","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1128\/JVI.02386-13","article-title":"The canarypox virus vector ALVAC induces distinct cytokine responses compared to the vacciniavirus-based vectors MVA and NYVAC in rhesus monkeys","volume":"88","author":"Teigler","year":"2014","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/gene.2013.14","article-title":"Transcriptomic profiles of high and low antibody responders to smallpox vaccine","volume":"14","author":"Kennedy","year":"2013","journal-title":"Genes Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.virol.2014.06.010","article-title":"The genome sequence of ectromelia virus Naval and Cornell isolates fromoutbreaks in North America","volume":"462\u2013463","author":"Mavian","year":"2014","journal-title":"Virology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15974","DOI":"10.1074\/jbc.270.27.15974","article-title":"Vaccinia virus B18R gene encodes a type I interferon-binding protein that blocks interferon alpha transmembrane signaling","volume":"270","author":"Colamonici","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0092-8674(95)90076-4","article-title":"Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity","volume":"81","author":"Symons","year":"1995","journal-title":"Cell"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/12\/692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:31:19Z","timestamp":1760196679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/12\/692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,5]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["v10120692"],"URL":"https:\/\/doi.org\/10.3390\/v10120692","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2018,12,5]]}}}