{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:32:14Z","timestamp":1778740334423,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003516","name":"Winn Feline Foundation","doi-asserted-by":"publisher","award":["W13-019"],"award-info":[{"award-number":["W13-019"]}],"id":[{"id":"10.13039\/100003516","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D10FE-303"],"award-info":[{"award-number":["D10FE-303"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate not only in enterocytes of the intestines but also in monocytes, subsequently systemically transporting the virus. The immune status and genetics of affected cats certainly play an important role in the pathogenesis. Considering the importance of genetics and host immune responses in viral infections, the goal of this study was to elucidate host gene expression in macrophages using RNA sequencing. Macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed a differential host gene expression. Despite the virus uptake, aligned viral reads did not increase from 2 to 17 h. The overlap of host gene expression among macrophages from different cats was limited, even though viral transcripts were detected in the cells. Interestingly, some of the downregulated genes in all macrophages were involved in immune signaling, while some upregulated genes common for all cats were found to be inhibiting immune activation. Our results highlight individual host responses playing an important role, consistent with the fact that few cats develop feline infectious peritonitis despite a common presence of enteric FCoV.<\/jats:p>","DOI":"10.3390\/cells9061431","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T08:49:11Z","timestamp":1591692551000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Host Gene Expression of Macrophages in Response to Feline Coronavirus Infection"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-8509","authenticated-orcid":false,"given":"Yvonne","family":"Drechsler","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5130-6622","authenticated-orcid":false,"given":"Elton J. R.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Leeds Omics, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Griggs","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro P. P. V.","family":"Diniz","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Collisson","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1136\/vr.130.7.133","article-title":"A study of naturally occurring feline coronavirus infections in kittens","volume":"130","author":"Addie","year":"1992","journal-title":"Vet. Rec."},{"key":"ref_2","first-page":"1449","article-title":"Serologic studies of naturally occurring feline infectious peritonitis","volume":"37","author":"Pedersen","year":"1976","journal-title":"Am. J. Vet. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jfms.2004.01.003","article-title":"Risk factors for feline coronavirus seropositivity in cats relinquished to a UK rescue charity","volume":"6","author":"Cave","year":"2004","journal-title":"J. Feline Med. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.cvsm.2011.08.004","article-title":"Feline coronavirus in multicat environments","volume":"41","author":"Drechsler","year":"2011","journal-title":"Vet. Clin. North. Am. Small Anim. Pract."},{"key":"ref_5","first-page":"368","article-title":"An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis","volume":"42","author":"Pedersen","year":"1981","journal-title":"Am. J. Vet. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.2460\/javma.1997.210.09.1313","article-title":"Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus","volume":"210","author":"Foley","year":"1997","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Olsen, R.G., Krakowka, S., and Blakeslee, J.R. (2019). Feline Infectious Peritonitis. Comparative Pathobiology of Viral Diseases, CRC Press.","DOI":"10.1201\/9780429286629"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1007\/s00705-005-0598-6","article-title":"Replication of feline coronaviruses in peripheral blood monocytes","volume":"150","author":"Dewerchin","year":"2005","journal-title":"Arch. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1099\/vir.0.020214-0","article-title":"Sites of feline coronavirus persistence in healthy cats","volume":"91","author":"Kipar","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1051\/vetres\/2010043","article-title":"Pathogenic characteristics of persistent feline enteric coronavirus infection in cats","volume":"41","author":"Vogel","year":"2010","journal-title":"Vet. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virusres.2011.12.020","article-title":"Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats","volume":"165","author":"Pedersen","year":"2012","journal-title":"Virus Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jfms.2005.04.003","article-title":"Prevalence of feline infectious peritonitis in specific cat breeds","volume":"8","author":"Radzai","year":"2006","journal-title":"J. Feline Med. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/j.1751-0813.2005.tb13044.x","article-title":"Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990\u20132002)","volume":"83","author":"Norris","year":"2005","journal-title":"Aust. Vet. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jfms.2010.09.014","article-title":"Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan","volume":"13","author":"Tsai","year":"2011","journal-title":"J. Feline Med. Surg"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1053\/rvsc.1999.0368","article-title":"Preliminary studies on feline coronavirus distribution in naturally and experimentally infected cats","volume":"68","author":"Kiss","year":"2000","journal-title":"Res. Vet. Sci"},{"key":"ref_16","first-page":"7","article-title":"An overview of feline enteric coronavirus and infectious peritonitis virus infections","volume":"23","author":"Pedersen","year":"1995","journal-title":"Feline Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1007\/s00705-017-3489-8","article-title":"Antibody-dependent enhancement of serotype II feline enteric coronavirus infection in primary feline monocytes","volume":"162","author":"Takano","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1292\/jvms.60.49","article-title":"Antibody-dependent enhancement of feline infectious peritonitis virus infection in feline alveolar macrophages and human monocyte cell line U937 by serum of cats experimentally or naturally infected with feline coronavirus","volume":"60","author":"Hohdatsu","year":"1998","journal-title":"J. Vet. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.vetmic.2006.08.033","article-title":"A \u201cpossible\u201d involvement of TNF-alpha in apoptosis induction in peripheral blood lymphocytes of cats with feline infectious peritonitis","volume":"119","author":"Takano","year":"2007","journal-title":"Vet. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.vetimm.2006.02.004","article-title":"Natural feline coronavirus infection: Differences in cytokine patterns in association with the outcome of infection","volume":"112","author":"Kipar","year":"2006","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetmic.2003.08.010","article-title":"In vivo cytokine response to experimental feline infectious peritonitis virus infection","volume":"97","author":"Dean","year":"2003","journal-title":"Vet. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jfms.2003.08.009","article-title":"Disease outcome and cytokine responses in cats immunized with an avirulent feline infectious peritonitis virus (FIPV)-UCD1 and challenge-exposed with virulent FIPV-UCD8","volume":"6","author":"Kiss","year":"2004","journal-title":"J. Feline Med. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1128\/JVI.79.2.1036-1044.2005","article-title":"Natural history of a recurrent feline coronavirus infection and the role of cellular immunity in survival and disease","volume":"79","year":"2005","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8977","DOI":"10.1128\/jvi.70.12.8977-8983.1996","article-title":"Apoptosis and T-cell depletion during feline infectious peritonitis","volume":"70","author":"Haagmans","year":"1996","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-1-4939-2438-7_20","article-title":"Transcriptome analysis of feline infectious peritonitis virus infection","volume":"1282","author":"Mehrbod","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/1743-422X-10-329","article-title":"Transcriptional profiling of feline infectious peritonitis virus infection in CRFK cells and in PBMCs from FIP diagnosed cats","volume":"10","author":"Harun","year":"2013","journal-title":"Virol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13567-018-0578-y","article-title":"Characterization of peritoneal cells from cats with experimentally-induced feline infectious peritonitis (FIP) using RNA-seq","volume":"49","author":"Watanabe","year":"2018","journal-title":"Vet. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1292\/jvms.10-0470","article-title":"A rapid and simple method to obtain canine peripheral blood-derived macrophages","volume":"73","author":"Ohno","year":"2011","journal-title":"J. Vet. Med. Sci"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_31","first-page":"e140","article-title":"Data quality aware analysis of differential expression in RNA-seq with NOISeq R\/Bioc package","volume":"43","author":"Tarazona","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/bioinformatics\/btq675","article-title":"Cytoscape 2.8: New features for data integration and network visualization","volume":"27","author":"Smoot","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.virusres.2018.06.010","article-title":"Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein","volume":"255","author":"Shirato","year":"2018","journal-title":"Virus Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1128\/jvi.63.1.436-440.1989","article-title":"Intrinsic resistance of feline peritoneal macrophages to coronavirus infection correlates with in vivo virulence","volume":"63","author":"Stoddart","year":"1989","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jfms.2008.09.008","article-title":"A review of feline infectious peritonitis virus infection: 1963-2008","volume":"11","author":"Pedersen","year":"2009","journal-title":"J. Feline Med. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1128\/jcm.34.12.3180-3184.1996","article-title":"Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus","volume":"34","author":"Poland","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1099\/jgv.0.000763","article-title":"Marek\u2019s disease virus infection of phagocytes: A de novo in vitro infection model","volume":"98","author":"Chakraborty","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.virusres.2011.03.027","article-title":"Vascular endothelial growth factor (VEGF), produced by feline infectious peritonitis (FIP) virus-infected monocytes and macrophages, induces vascular permeability and effusion in cats with FIP","volume":"158","author":"Takano","year":"2011","journal-title":"Virus Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/mi.2017.77","article-title":"Epithelial-derived TGF-beta1 acts as a pro-viral factor in the lung during influenza A infection","volume":"11","author":"Denney","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_43","first-page":"2458","article-title":"HAUS8 regulates RLRVISA antiviral signaling positively by targeting VISA","volume":"18","author":"He","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1128\/JVI.73.1.290-296.1999","article-title":"RNase L inhibitor is induced during human immunodeficiency virus type 1 infection and down regulates the 2-5A\/RNase L pathway in human T cells","volume":"73","author":"Martinand","year":"1999","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1074\/mcp.M116.057984","article-title":"Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages","volume":"15","author":"Soderholm","year":"2016","journal-title":"Mol. Cell Proteomics"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chang, C.K., Chen, C.J., Wu, C.C., Chen, S.W., Shih, S.R., and Kuo, R.L. (2017). Cellular hnRNP A2\/B1 interacts with the NP of influenza A virus and impacts viral replication. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188214"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1080\/15476286.2019.1629208","article-title":"Strand-specific affinity of host factor hnRNP C1\/C2 guides positive to negative-strand ratio in Coxsackievirus B3 infection","volume":"16","author":"Dave","year":"2019","journal-title":"RNA Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1128\/JVI.00079-11","article-title":"Ubiquitin-specific peptidase 20 targets TRAF6 and human T cell leukemia virus type 1 tax to negatively regulate NF-kappaB signaling","volume":"85","author":"Yasunaga","year":"2011","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nri2938","article-title":"Immune cell regulation by autocrine purinergic signalling","volume":"11","author":"Junger","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.micinf.2012.05.010","article-title":"Multifaceted roles of purinergic receptors in viral infection","volume":"14","author":"Paoletti","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Burbage, M., Gasparrini, F., Aggarwal, S., Gaya, M., Arnold, J., Nair, U., Way, M., Bruckbauer, A., and Batista, F.D. (2018). Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity. Elife, 7.","DOI":"10.7554\/eLife.26556"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11804","DOI":"10.3390\/ijms130911804","article-title":"Modification by ubiquitin-like proteins: Significance in apoptosis and autophagy pathways","volume":"13","author":"Cajee","year":"2012","journal-title":"Int. J. Mol. Sci"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"35521","DOI":"10.1038\/srep35521","article-title":"Interferon Regulatory Factor 4 controls TH1 cell effector function and metabolism","volume":"6","author":"Mahnke","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1089\/aid.2006.0100","article-title":"Leukemia inhibitor factor (LIF) inhibits HIV-1 replication via restriction of stat 3 activation","volume":"23","author":"Tjernlund","year":"2007","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1128\/JVI.79.4.2079-2086.2005","article-title":"Inhibition of Beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3","volume":"79","author":"Spiegel","year":"2005","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1742-4690-4-27","article-title":"Centrosome and retroviruses: The dangerous liaisons","volume":"4","author":"Afonso","year":"2007","journal-title":"Retrovirology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41564-018-0285-5","article-title":"Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear lamina integrity","volume":"4","author":"Full","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Naghavi, M.H., and Walsh, D. (2017). Microtubule Regulation and Function during Virus Infection. J. Virol., 91.","DOI":"10.1128\/JVI.00538-17"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.1172\/JCI59492","article-title":"T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice","volume":"121","author":"Wiede","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_60","first-page":"4012","article-title":"SP140 regulates the expression of immune-related genes associated with multiple sclerosis and other autoimmune diseases by NF-kappaB inhibition","volume":"27","author":"Karaky","year":"2018","journal-title":"Hum. Mol. Genet."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/6\/1431\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:37:03Z","timestamp":1760175423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/6\/1431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cells9061431"],"URL":"https:\/\/doi.org\/10.3390\/cells9061431","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]}}}