{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:11:21Z","timestamp":1783476681923,"version":"3.55.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFD0500100"],"award-info":[{"award-number":["2016YFD0500100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31500703"],"award-info":[{"award-number":["31500703"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAU-Grant for the Prevention and Control of Immunosuppressive Diseases in Animals","award":["2020"],"award-info":[{"award-number":["2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alphaherpesviruses are large dsDNA viruses with an ability to establish persistent infection in hosts, which rely partly on their ability to evade host innate immune responses, notably the type I IFN response. However, the relevant molecular mechanisms are not well understood. In this study, we report the UL42 proteins of alphaherpesvirus pseudorabies virus (PRV) and HSV type 1 (HSV1) as a potent antagonist of the IFN-I\u2013induced JAK-STAT signaling pathway. We found that ectopic expression of UL42 in porcine macrophage CRL and human HeLa cells significantly suppresses IFN-\u03b1\u2013mediated activation of the IFN-stimulated response element (ISRE), leading to a decreased transcription and expression of IFN-stimulated genes (ISGs). Mechanistically, UL42 directly interacts with ISRE and interferes with ISG factor 3 (ISGF3) from binding to ISRE for efficient gene transcription, and four conserved DNA-binding sites of UL42 are required for this interaction. The substitution of these DNA-binding sites with alanines results in reduced ISRE-binding ability of UL42 and impairs for PRV to evade the IFN response. Knockdown of UL42 in PRV remarkably attenuates the antagonism of virus to IFN in porcine kidney PK15 cells. Our results indicate that the UL42 protein of alphaherpesviruses possesses the ability to suppress IFN-I signaling by preventing the association of ISGF3 and ISRE, thereby contributing to immune evasion. This finding reveals UL42 as a potential antiviral target.<\/jats:p>","DOI":"10.4049\/jimmunol.2001306","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T17:05:19Z","timestamp":1626455119000},"page":"613-625","source":"Crossref","is-referenced-by-count":28,"title":["Pseudorabies Virus DNA Polymerase Processivity Factor UL42 Inhibits Type I IFN Response by Preventing ISGF3-ISRE Interaction"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9015-0819","authenticated-orcid":false,"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Qin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuilian","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3003-7421","authenticated-orcid":false,"given":"Yunfan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liankai","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7273-5132","authenticated-orcid":false,"given":"Xinrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences , Hangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"2025022608110892100_r1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1128\/CMR.14.4.778-809.2001","article-title":"Antiviral actions of interferons","volume":"14","author":"Samuel","year":"2001","journal-title":"Clin. 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