{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:06:05Z","timestamp":1759935965721},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T00:00:00Z","timestamp":1446076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T00:00:00Z","timestamp":1446076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Viral cycle progression depends upon host-cell processes in infected cells and this is true for bovine viral diarrhoea virus (BVDV), the causative agent of BVD that is a worldwide threat to the bovine industry. Heme oxygenase-1 (HO-1) is a ubiquitously expressed inducible isoform of the first and rate-limiting enzyme for heme degradation. Recent studies have demonstrated that HO-1 has significant antiviral properties, inhibiting the replication of viruses such as ebola virus, human immunodeficiency virus, hepatitis C virus and porcine reproductive and respiratory syndrome virus. However, the function of HO-1 in BVDV infection is unclear. In the present study, the relationship between HO-1 and BVDV was investigated. <jats:italic>In vitro<\/jats:italic> analysis of HO-1 expression in BVDV-infected MDBK cells demonstrated that a decrease in HO-1 as BVDV replication increased. Increasing HO-1 expression through adenoviral-mediated overexpression or induction with cobalt protoporphyrin (CoPP, a potent HO-1 inducer), pre- and postinfection, effectively inhibited BVDV replication. In contrast, HO-1 siRNA knockdown in BVDV-infected cells increased BVDV replication. Therefore, the data were consistent with HO-1 acting as an anti-viral factor and these findings suggested that induction of HO-1 may be a useful prevention and treatment strategy against BVDV infection.<\/jats:p>","DOI":"10.1038\/srep15575","type":"journal-article","created":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T09:59:23Z","timestamp":1446112763000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Heme Oxygenase-1 Suppresses Bovine Viral Diarrhoea Virus Replication in vitro"],"prefix":"10.1038","volume":"5","author":[{"given":"Chong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengxing","family":"Pu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lele","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhuan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongliang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaiping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian G.","family":"Goodfellow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"En-Min","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuqi","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,10,29]]},"reference":[{"key":"BFsrep15575_CR1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.meegid.2014.01.003","volume":"28","author":"A Chernick","year":"2014","unstructured":"Chernick, A., Godson, D. L. & van der Meer, F. Metadata beyond the sequence enables the phylodynamic inference of bovine viral diarrhea virus type 1a isolates from Western Canada. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 28, 367\u2013374 (2014).","journal-title":"Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases"},{"key":"BFsrep15575_CR2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1128\/JVI.06968-11","volume":"87","author":"E Curti","year":"2013","unstructured":"Curti, E. & Jaeger, J. Residues Arg283, Arg285 and Ile287 in the nucleotide binding pocket of bovine viral diarrhea virus NS5B RNA polymerase affect catalysis and fidelity. Journal of virology 87, 199\u2013207 (2013).","journal-title":"Journal of virology"},{"key":"BFsrep15575_CR3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.prevetmed.2005.07.018","volume":"72","author":"A Lindberg","year":"2005","unstructured":"Lindberg, A. & Houe, H. Characteristics in the epidemiology of bovine viral diarrhea virus (BVDV) of relevance to control. Preventive veterinary medicine 72, 55\u201373, discussion 215\u2013219 (2005).","journal-title":"Preventive veterinary medicine"},{"key":"BFsrep15575_CR4","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.vetmic.2009.09.049","volume":"142","author":"H Van Campen","year":"2010","unstructured":"Van Campen, H. Epidemiology and control of BVD in the U.S. Veterinary microbiology 142, 94\u201398 (2010).","journal-title":"Veterinary microbiology"},{"key":"BFsrep15575_CR5","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.vetmic.2012.04.023","volume":"159","author":"Y Deng","year":"2012","unstructured":"Deng, Y. et al. High prevalence of bovine viral diarrhea virus 1 in Chinese swine herds. Veterinary microbiology 159, 490\u2013493 (2012).","journal-title":"Veterinary microbiology"},{"key":"BFsrep15575_CR6","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1073\/pnas.61.2.748","volume":"61","author":"R Tenhunen","year":"1968","unstructured":"Tenhunen, R., Marver, H. S. & Schmid, R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America 61, 748\u2013755 (1968).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep15575_CR7","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1042\/CS20110147","volume":"122","author":"A Grochot-Przeczek","year":"2012","unstructured":"Grochot-Przeczek, A., Dulak, J. & Jozkowicz, A. Haem oxygenase-1: non-canonical roles in physiology and pathology. Clin Sci (Lond) 122, 93\u2013103 (2012).","journal-title":"Clin Sci (Lond)"},{"key":"BFsrep15575_CR8","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/j.1462-5822.2008.01261.x","volume":"11","author":"SW Chung","year":"2009","unstructured":"Chung, S. W., Hall, S. R. & Perrella, M. A. Role of haem oxygenase-1 in microbial host defence. Cellular microbiology 11, 199\u2013207 (2009).","journal-title":"Cellular microbiology"},{"key":"BFsrep15575_CR9","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fphar.2012.00129","volume":"3","author":"WN Schmidt","year":"2012","unstructured":"Schmidt, W. N., Mathahs, M. M. & Zhu, Z. Heme and HO-1 Inhibition of HCV, HBV and HIV. Frontiers in pharmacology 3, 129 (2012).","journal-title":"Frontiers in pharmacology"},{"key":"BFsrep15575_CR10","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1002\/hep.22491","volume":"48","author":"Z Zhu","year":"2008","unstructured":"Zhu, Z. et al. Heme oxygenase-1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury. Hepatology 48, 1430\u20131439 (2008).","journal-title":"Hepatology"},{"key":"BFsrep15575_CR11","doi-asserted-by":"publisher","first-page":"4252","DOI":"10.4049\/jimmunol.176.7.4252","volume":"176","author":"K Devadas","year":"2006","unstructured":"Devadas, K. & Dhawan, S. Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction. Journal of immunology 176, 4252\u20134257 (2006).","journal-title":"Journal of immunology"},{"key":"BFsrep15575_CR12","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1053\/j.gastro.2007.07.021","volume":"133","author":"U Protzer","year":"2007","unstructured":"Protzer, U. et al. Antiviral activity and hepatoprotection by heme oxygenase-1 in hepatitis B virus infection. Gastroenterology 133, 1156\u20131165 (2007).","journal-title":"Gastroenterology"},{"key":"BFsrep15575_CR13","doi-asserted-by":"publisher","first-page":"13795","DOI":"10.1128\/JVI.02422-13","volume":"87","author":"L Hill-Batorski","year":"2013","unstructured":"Hill-Batorski, L., Halfmann, P., Neumann, G. & Kawaoka, Y. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication. Journal of virology 87, 13795\u201313802 (2013).","journal-title":"Journal of virology"},{"key":"BFsrep15575_CR14","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.antiviral.2014.07.011","volume":"110","author":"S Xiao","year":"2014","unstructured":"Xiao, S. et al. Heme oxygenase-1 acts as an antiviral factor for porcine reproductive and respiratory syndrome virus infection and over-expression inhibits virus replication in vitro. Antiviral research 110, 60\u201369 (2014).","journal-title":"Antiviral research"},{"key":"BFsrep15575_CR15","doi-asserted-by":"publisher","first-page":"4527","DOI":"10.1128\/JVI.02810-14","volume":"89","author":"S Xiao","year":"2015","unstructured":"Xiao, S. et al. MiR-24-3p Promotes Porcine Reproductive and Respiratory Syndrome Virus Replication through Suppression of Heme Oxygenase-1 Expression. Journal of virology 89, 4527\u20134538 (2015).","journal-title":"Journal of virology"},{"key":"BFsrep15575_CR16","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.virusres.2013.01.012","volume":"173","author":"Z Shi","year":"2013","unstructured":"Shi, Z. et al. Down-regulation of cellular protein heme oxygenase 1 inhibits proliferation of classical swine fever virus in PK-15 cells. Virus research 173, 315\u2013320 (2013).","journal-title":"Virus research"},{"key":"BFsrep15575_CR17","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1099\/vir.0.052142-0","volume":"94","author":"J Lee","year":"2013","unstructured":"Lee, J., Koh, K., Kim, Y. E., Ahn, J. H. & Kim, S. Upregulation of Nrf2 expression by human cytomegalovirus infection protects host cells from oxidative stress. The Journal of general virology 94, 1658\u20131668 (2013).","journal-title":"The Journal of general virology"},{"key":"BFsrep15575_CR18","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jhep.2005.12.020","volume":"45","author":"T Ghaziani","year":"2006","unstructured":"Ghaziani, T. et al. HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells. Journal of hepatology 45, 5\u201312 (2006).","journal-title":"Journal of hepatology"},{"key":"BFsrep15575_CR19","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.fsi.2011.11.019","volume":"32","author":"J Yuan","year":"2012","unstructured":"Yuan, J. et al. Down-regulation of heme oxygenase-1 by SVCV infection. Fish & shellfish immunology 32, 301\u2013306 (2012).","journal-title":"Fish & shellfish immunology"},{"key":"BFsrep15575_CR20","doi-asserted-by":"publisher","first-page":"3316","DOI":"10.1002\/jcp.22677","volume":"226","author":"WH Tung","year":"2011","unstructured":"Tung, W. H., Hsieh, H. L., Lee, I. T. & Yang, C. M. Enterovirus 71 induces integrin beta1\/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: role of HO-1\/CO in viral replication. Journal of cellular physiology 226, 3316\u20133329 (2011).","journal-title":"Journal of cellular physiology"},{"key":"BFsrep15575_CR21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.antiviral.2014.02.010","volume":"105","author":"L Wang","year":"2014","unstructured":"Wang, L. et al. Inhibition of replication of porcine reproductive and respiratory syndrome virus by hemin is highly dependent on heme oxygenase-1, but independent of iron in MARC-145 cells. Antiviral research 105, 39\u201346 (2014).","journal-title":"Antiviral research"},{"key":"BFsrep15575_CR22","doi-asserted-by":"publisher","first-page":"e11377","DOI":"10.1371\/journal.pone.0011377","volume":"5","author":"S Xiao","year":"2010","unstructured":"Xiao, S. et al. Understanding PRRSV infection in porcine lung based on genome-wide transcriptome response identified by deep sequencing. PloS one 5, e11377 (2010).","journal-title":"PloS one"},{"key":"BFsrep15575_CR23","doi-asserted-by":"publisher","first-page":"4459","DOI":"10.1172\/JCI72279","volume":"124","author":"AJ Gill","year":"2014","unstructured":"Gill, A. J. et al. Heme oxygenase-1 deficiency accompanies neuropathogenesis of HIV-associated neurocognitive disorders. The Journal of clinical investigation 124, 4459\u20134472 (2014).","journal-title":"The Journal of clinical investigation"},{"key":"BFsrep15575_CR24","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1086\/423488","volume":"190","author":"MY Abdalla","year":"2004","unstructured":"Abdalla, M. Y. et al. Down-regulation of heme oxygenase-1 by hepatitis C virus infection in vivo and by the in vitro expression of hepatitis C core protein. The Journal of infectious diseases 190, 1109\u20131118 (2004).","journal-title":"The Journal of infectious diseases"},{"key":"BFsrep15575_CR25","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ejim.2012.05.001","volume":"23","author":"MY Abdalla","year":"2012","unstructured":"Abdalla, M. Y., Mathahs, M. M. & Ahmad, I. M. Reduced heme oxygenase-1 expression in steatotic livers infected with hepatitis C virus. European journal of internal medicine 23, 649\u2013655 (2012).","journal-title":"European journal of internal medicine"},{"key":"BFsrep15575_CR26","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.bbrc.2013.04.095","volume":"435","author":"ZH Zhou","year":"2013","unstructured":"Zhou, Z. H. et al. Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages. Biochemical and biophysical research communications 435, 373\u2013377 (2013).","journal-title":"Biochemical and biophysical research communications"},{"key":"BFsrep15575_CR27","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1038\/sj.gt.3301540","volume":"8","author":"T Hashiba","year":"2001","unstructured":"Hashiba, T. et al. Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice. Gene therapy 8, 1499\u20131507 (2001).","journal-title":"Gene therapy"},{"key":"BFsrep15575_CR28","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1002\/hep.23339","volume":"51","author":"E Lehmann","year":"2010","unstructured":"Lehmann, E. et al. The heme oxygenase 1 product biliverdin interferes with hepatitis C virus replication by increasing antiviral interferon response. Hepatology 51, 398\u2013404 (2010).","journal-title":"Hepatology"},{"key":"BFsrep15575_CR29","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1186\/1743-422X-8-491","volume":"8","author":"S Xiao","year":"2011","unstructured":"Xiao, S. et al. Inhibition of highly pathogenic PRRSV replication in MARC-145 cells by artificial microRNAs. Virology journal 8, 491 (2011).","journal-title":"Virology journal"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep15575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep15575","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep15575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T14:43:22Z","timestamp":1672929802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep15575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,29]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,7]]}},"alternative-id":["BFsrep15575"],"URL":"https:\/\/doi.org\/10.1038\/srep15575","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,29]]},"assertion":[{"value":"10 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15575"}}