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Previous studies from other groups showed that CD163 is required for PRRSV uncoating and genome release. However, CD163 does not interact with nucleocapsid (N) protein. In this study, the neonatal Fc receptor (FcRn) was demonstrated to be irreplaceable for PRRSV infection by knockdown, overexpression, antibodies or IgG blocking, knockout, and replenishment assays. FcRn was further revealed to be involved in PRRSV uncoating for the first time rather than viral attachment and internalization. In detail, FcRn was determined to colocalize with CD163 and PRRSV virions in early endosomes and specially interact with N protein in early endosomes. Taken together, these results provide evidence that FcRn is an essential cellular factor for PRRSV uncoating, which will be a promising target to interfere with the viral infection.<\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                PRRSV infection results in a severe swine disease affecting pig farming in the world. Although CD163 has been implicated as the uncoating receptor for PRRSV but the uncoating mechanism of PRRSV remains unclear. Here, we identified that FcRn facilitated virion uncoating\n                <jats:italic>via<\/jats:italic>\n                interaction with viral N protein in early endosomes. Our work actually expands the knowledge of PRRSV infection and provides an attractive therapeutic target for the prevention and control of PRRS.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01218-24","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T14:00:26Z","timestamp":1733752826000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["The neonatal Fc receptor (FcRn) is required for porcine reproductive and respiratory syndrome virus uncoating"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7958-4347","authenticated-orcid":false,"given":"Kang","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiarui","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangchao","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijian","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weida","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-1339","authenticated-orcid":true,"given":"Zili","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1135(96)01326-0"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063879200400201"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.2460\/javma.2005.227.385"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/01652176.1991.9694296"},{"key":"e_1_3_5_6_2","volume-title":"International Committee on Taxonomy of Viruses (ICTV), release EC50","author":"ICTV","year":"2018","unstructured":"ICTV. 2018. 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