{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:26:59Z","timestamp":1760243219931,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T00:00:00Z","timestamp":1415577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p> Japanese encephalitis virus (JEV) is one of the pathogens that can invade the central nervous system, causing acute infection and inflammation of brain. SOCS3 protein plays a vital role in immune processes and inflammation of the central nervous system. In this study, Raw264.7 cells and suckling mice were infected with JEV, and SOCS3 expression was analyzed by the gene expression profile, semiquantitative RT-PCR, qRT-PCR, immunohistochemistry (IHC) and Western blot. Results indicated that 520 genes were found to be differentially expressed (fold change \u2265 2.0, p &lt; 0.05) in total. The differentially regulated genes were involved in biological processes, such as stimulus response, biological regulation and immune system processes. JEV early infection could induce SOCS3 expression, upregulating both the mRNA and protein levels in Raw264.7 cells in a time-dependent manner. The SOCS3 expression was much lower in Raw264.7 cells infected with inactivated JEV than wild-type JEV. In vivo, SOCS3 protein was also found to upregulate the expression of mRNA and protein in JEV-infected mouse brain. Taken together, our data showed that JEV early infection could induce the upregulation of SOCS3 expression, both in vitro and in vivo, providing the basic theoretical foundation for future research on the invasion mechanism of JEV.<\/jats:p>","DOI":"10.3390\/v6114280","type":"journal-article","created":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T12:23:05Z","timestamp":1415622185000},"page":"4280-4293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Japanese Encephalitis Virus Upregulates the Expression of SOCS3 in Mouse Brain and Raw264.7 Cells"],"prefix":"10.3390","volume":"6","author":[{"given":"Xiangmin","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qishu","family":"Cao","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Qian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, Hubei, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/0264-410X(94)90329-8","article-title":"Towards a new generation of flavivirus vaccines","volume":"12","author":"Venugopal","year":"1994","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.4161\/hv.26902","article-title":"Japanese Encephalitis: The virus and vaccines","volume":"10","author":"Yun","year":"2013","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e437","DOI":"10.1371\/journal.pntd.0000437","article-title":"Japanese Encephalitis-Pathological and Clinical Perspective","volume":"3","author":"Ghosh","year":"2009","journal-title":"PLoS. Negl. Trop. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2217\/14796708.3.5.515","article-title":"Japanese encephalitis: Perspective and new developments","volume":"3","author":"Saxena","year":"2008","journal-title":"Future Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/1743-422X-10-258","article-title":"Japanese encephalitis virus infects porcine kidney epithelial PK15 cells via clathrin- and cholesterol-dependent endocytosis","volume":"10","author":"Yang","year":"2013","journal-title":"Virol. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1743-422X-8-80","article-title":"Japanese encephalitis virus infection induces changes of mRNA profile of mouse spleen and brain","volume":"8","author":"Yang","year":"2011","journal-title":"Virol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/vir.0.83391-0","article-title":"Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures","volume":"89","author":"Randall","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_8","first-page":"315","article-title":"Pathogenic viruses: Smart manipulators of the interferon system","volume":"316","author":"Haller","year":"2007","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/JVI.73.1.783-786.1999","article-title":"New mouse model for dengue virus vaccine testing","volume":"73","author":"Johnson","year":"1999","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1128\/JVI.74.11.4957-4966.2000","article-title":"Modulation of Dengue virus infection in human cells by alpha, beta, and gamma interferons","volume":"74","author":"Diamond","year":"2000","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9285","DOI":"10.1128\/JVI.78.17.9285-9294.2004","article-title":"Blocking of the alpha interferon-induced Jak-Stat signaling pathway by Japanese encephalitis virus infection","volume":"78","author":"Lin","year":"2004","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5908","DOI":"10.1128\/JVI.02714-05","article-title":"Blocking of interferon-induced Jak-Stat signaling by Japanese encephalitis virus NS5 through a protein tyrosine phosphatase-mediated mechanism","volume":"80","author":"Lin","year":"2006","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.it.2009.07.001","article-title":"SOCS1 and SOCS3 in the control of CNS immunity","volume":"30","author":"Baker","year":"2009","journal-title":"Trends. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.semcdb.2008.07.010","article-title":"SOCS regulation of the JAK\/STAT signalling pathway","volume":"19","author":"Croker","year":"2008","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nri1226","article-title":"Regulation of JAK-STAT signalling in the immune system","volume":"3","author":"Shuai","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.4049\/jimmunol.0903563","article-title":"Suppressor of cytokine signaling 3 inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages","volume":"185","author":"Akhtar","year":"2010","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1042\/BST20130077","article-title":"Regulation of Janus kinases by SOCS proteins","volume":"41","author":"Kershaw","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev.immunol.22.091003.090312","article-title":"The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response","volume":"22","author":"Alexander","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5966","DOI":"10.4049\/jimmunol.179.9.5966","article-title":"Molecular mechanism of lipopolysaccharide-induced SOCS-3 gene expression in macrophages and microglia","volume":"179","author":"Qin","year":"2007","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.cellimm.2013.09.005","article-title":"Japanese encephalitis virus infection modulates the expression of suppressors of cytokine signaling (SOCS) in macrophages: Implications for the hosts\u2019 innate immune response","volume":"285","author":"Kundu","year":"2013","journal-title":"Cell. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1186\/1743-422X-8-472","article-title":"Isolation and molecular characterization of genotype 1 Japanese encephalitis virus, SX09S-01, from pigs in China","volume":"8","author":"Cao","year":"2011","journal-title":"Virol. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1128\/JVI.01857-10","article-title":"Viral exploitation of host SOCS protein functions","volume":"85","author":"Akhtar","year":"2011","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1172\/JCI16491","article-title":"The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury","volume":"111","author":"Yasukawa","year":"2003","journal-title":"J. Clin. Invest."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1096\/fj.02-0664fje","article-title":"IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3","volume":"17","author":"Bode","year":"2003","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.virusres.2009.12.003","article-title":"Hepatitis B virus overexpresses suppressor of cytokine signaling-3 (SOCS3) thereby contributing to severity of inflammation in the liver","volume":"148","author":"Koeberlein","year":"2010","journal-title":"Virus Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1128\/JVI.78.12.6282-6286.2004","article-title":"Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway","volume":"78","author":"Yokota","year":"2004","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.virol.2005.04.028","article-title":"Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 confers efficient viral replication","volume":"338","author":"Yokota","year":"2005","journal-title":"Virology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.jinf.2006.06.005","article-title":"Respiratory syncytial virus inhibits interferon-alpha-inducible signaling in macrophage-like U937 cells","volume":"54","author":"Zhao","year":"2007","journal-title":"J. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.virol.2009.06.026","article-title":"RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules","volume":"391","author":"Hashimoto","year":"2009","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1000196","DOI":"10.1371\/journal.ppat.1000196","article-title":"Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression","volume":"4","author":"Pauli","year":"2008","journal-title":"PLoS Pathog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.4049\/jimmunol.180.4.2034","article-title":"Cutting edge: Innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I\/IFNAR1-dependent pathway","volume":"180","author":"Pothlichet","year":"2008","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1089\/vbz.2009.0259","article-title":"Transcriptional upregulation of SOCS 1 and suppressors of cytokine signaling 3 mRNA in the absence of suppressors of cytokine signaling 2 mRNA after infection with West Nile virus or tick-borne encephalitis virus","volume":"10","author":"Mansfield","year":"2010","journal-title":"Vector Borne Zoonotic Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/11\/4280\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:09:09Z","timestamp":1760216949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/11\/4280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,10]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11]]}},"alternative-id":["v6114280"],"URL":"https:\/\/doi.org\/10.3390\/v6114280","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2014,11,10]]}}}