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In this study, we showed that FMDV infection activated two unfolded protein response branches (PERK-eIF2\u03b1 and ATF6 signaling) in both baby hamster kidney cells (BHK-21) and porcine kidney (PK-15) cells, whereas it suppressed the IRE1\u03b1-XBP1 signaling by decreasing IRE1\u03b1 level. Further study revealed IRE1\u03b1 signaling as an important antiviral innate immune mechanism against FMDV. Sec62, the transport protein, was greatly decreased at the late stages of FMDV infection. By overexpression and knockdown study, we also found that the expression of Sec62 was positively involved in the levels of IRE1\u03b1 and RIG-I and subsequent activation of downstream antiviral signaling pathways in FMDV-infected PK-15 cells. Taken together, our study demonstrates that Sec62 is an important antiviral factor that upregulates IRE1\u03b1\u2013RIG-I\u2013dependent antiviral innate immune responses, and FMDV evades antiviral host defense mechanism by downregulating Sec62-IRE1\u03b1\/RIG-I.<\/jats:p>","DOI":"10.4049\/jimmunol.1801546","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T19:35:13Z","timestamp":1559763313000},"page":"429-440","source":"Crossref","is-referenced-by-count":12,"title":["Sec62 Suppresses Foot-and-Mouth Disease Virus Proliferation by Promotion of IRE1\u03b1\u2013RIG-I Antiviral Signaling"],"prefix":"10.1093","volume":"203","author":[{"given":"Shichong","family":"Han","sequence":"first","affiliation":[{"name":"World Organisation for Animal Health\u2013China National Foot-and-Mouth Disease Reference Laboratory, State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou 730046, Gansu ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6044-4971","authenticated-orcid":false,"given":"Lejiao","family":"Mao","sequence":"additional","affiliation":[{"name":"World Organisation for Animal Health\u2013China National Foot-and-Mouth Disease Reference Laboratory, State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou 730046, Gansu ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Shanghai 200241 ,","place":["People\u2019s Republic of 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