{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:53:34Z","timestamp":1781560414405,"version":"3.54.5"},"reference-count":40,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T00:00:00Z","timestamp":1443484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Interferon &amp; Cytokine Research"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>\n                    The genetic regulatory network controlling the innate immune system is well understood in many species. However, the role of the epigenetic mechanisms underlying the expression of immunoregulatory genes is less clear, especially in livestock species. Histone H3 lysine 9 dimethylation (H3K9me2) is an epigenetic modification associated with transcriptional silencing within the euchromatin regions. Euchromatic histone-lysine N-methyltransferase 2 (EHMT2; also known as G9a) is a crucial enzyme responsible for regulating the dynamics of this epigenetic modification. It has been shown that histone modifications play a role in regulating type I interferon (IFN) response. In the present study, we investigated the role of EHMT2 in the epigenetic regulation of bovine antiviral innate immunity and explored its therapeutic potential against viral infections. We evaluated the effects of pharmacological and RNAi-mediated inhibition of EHMT2 on the transcription of\n                    <jats:italic toggle=\"yes\">IFN-\u03b2<\/jats:italic>\n                    and other IFN-inducible antiviral genes, as well as its effect on foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus (VSV) replication in bovine cells. We show that treatment of primary bovine cells with the synthetic EHMT2 inhibitor (UNC0638) either before or shortly after virus infection resulted in a significant increase in transcript levels of bovine\n                    <jats:italic toggle=\"yes\">IFN-\u03b2<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">boIFN-\u03b2<\/jats:italic>\n                    ; 300-fold) and other IFN-inducible genes, including IFN-stimulated gene 15 (ISG-15), myxovirus resistance 1 (\n                    <jats:italic toggle=\"yes\">Mx-1<\/jats:italic>\n                    ),\n                    <jats:italic toggle=\"yes\">Mx-2<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">RIG-I<\/jats:italic>\n                    , 2\u2032,5\u2032-oligoadenylate synthetase 1 (\n                    <jats:italic toggle=\"yes\">OAS-1<\/jats:italic>\n                    ), and protein kinase R (\n                    <jats:italic toggle=\"yes\">PKR<\/jats:italic>\n                    ). Expression of these factors correlated with a significant decrease in VSV and FMDV viral titers. Our data confirm the involvement of EHMT2 in the epigenetic regulation of\n                    <jats:italic toggle=\"yes\">boIFN-\u03b2<\/jats:italic>\n                    and demonstrate the activation of a general antiviral state after EHMT2 inhibition.\n                  <\/jats:p>","DOI":"10.1089\/jir.2015.0006","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T16:08:20Z","timestamp":1443542900000},"page":"37-47","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Inhibition of EHMT2 Induces a Robust Antiviral Response Against Foot-and-Mouth Disease and Vesicular Stomatitis Virus Infections in Bovine Cells"],"prefix":"10.1177","volume":"36","author":[{"given":"Neetu","family":"Singh","sequence":"first","affiliation":[{"name":"Texas A&M University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth","family":"Ram\u0129rez-Carvajal","sequence":"additional","affiliation":[{"name":"Texas A&M University"},{"name":"Oak Ridge Institute for Science and Education (ORISE)-Plum Island Animal Disease Center (PIADC) Research Participation Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"de los Santos","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center (PIADC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Golding","sequence":"additional","affiliation":[{"name":"Texas A&M University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Long","sequence":"additional","affiliation":[{"name":"Texas A&M University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,9,29]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00169-0"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00503-5"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.8.4838-4847.2005"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1837309"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5498-5503.2001"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.1621-1625.2003"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01874-09"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050240"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.10.e46"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112343"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2010.01587.x"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(00)00359-8"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.03.014"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2007.06.003"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.103531"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002037"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.017"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737310"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-07-0114"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205414109"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1179438"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.38"},{"key":"e_1_3_3_25_1","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed LJ","year":"1938","unstructured":"Reed LJ, and Muench H. 1938. 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