{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:45:45Z","timestamp":1788302745709,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs of all ages. PEDV can be grouped into G1 (classical strains) and G2 (variant strains) based on sequence differences in the spike gene. Although several pathogenesis studies using contemporary strains of PEDV have been conducted to date, there is limited information on the pathogenesis of historical PEDV strains in contemporary pigs. This study aimed to investigate the clinical disease course of 10\u2009days-old pigs infected with a classical European G1a PEDV strain from the 1980s which was last passaged in pigs in 1994.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sequencing results confirmed that the virus inoculum was a PEDV strain closely related to the prototype CV777 strain. The PEDV stock was serially passaged three times in Vero cells, and the P3 infectious virus stock was used to inoculate the pigs. A total of 40 pigs were inoculated using the oral route.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pigs showed no enteric disease signs, and PEDV shedding was not detected for 44\u2009days post-inoculation (dpi). At necropsy at 3 (5 pigs) or 7 dpi (5 pigs), no lesions were observed in intestinal sections, which were negative for PEDV antigen by immunohistochemistry. In addition, no IgG or IgA PEDV-specific antibodies in serum or fecal samples for 35 dpi further indicates a lack of infection. Titration of the leftover thawed and refrozen PEDV virus stock inoculum showed that the virus stock retained its infectivity in Vero cell culture and the porcine small intestine enterocytes cell line IPEC-J2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The reasons for the loss of infectivity in pigs are unknown. In conclusion, we showed that a classical G1a PEDV strain successfully propagated in cell cultures could not orally infect 40 piglets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2023.1279162","type":"journal-article","created":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T21:13:28Z","timestamp":1700428408000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Failure to experimentally infect 10\u2009days-old piglets with a cell culture-propagated infectious stock of a classical genotype 1a porcine epidemic diarrhea virus"],"prefix":"10.3389","volume":"10","author":[{"given":"Priscilla F.","family":"Gerber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianjun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Ting","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Lager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berend Jan","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Jin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick G.","family":"Halbur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Opriessnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"198045","DOI":"10.1016\/j.virusres.2020.198045","article-title":"Porcine epidemic diarrhea virus (PEDV): an update on etiology, transmission, pathogenesis, and prevention and control","volume":"286","author":"Jung","year":"2020","journal-title":"Virus Res"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001843","article-title":"ICTV virus taxonomy profile: Coronaviridae 2023","volume":"104","author":"Woo","year":"2023","journal-title":"J Gen Virol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/tbed.12991","article-title":"Evolutionary and genotypic analyses of global porcine epidemic diarrhea virus strains","volume":"66","author":"Guo","year":"2019","journal-title":"Transbound Emerg Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"790","DOI":"10.3390\/v12080790","article-title":"Molecular characterization of porcine epidemic diarrhea virus and its new genetic classification based on the nucleocapsid gene","volume":"12","author":"Kim","year":"2020","journal-title":"Viruses"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.virusres.2016.05.030","article-title":"Porcine epidemic diarrhea: a retrospect from Europe and matters of debate","volume":"226","author":"Pensaert","year":"2016","journal-title":"Virus Res"},{"key":"ref6","first-page":"219","article-title":"Experimental infection of pigs with a new porcine enteric coronavirus, CV 777","volume":"41","author":"Debouck","year":"1980","journal-title":"Am J Vet Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.virusres.2016.05.026","article-title":"Porcine epidemic diarrhea in China","volume":"226","author":"Wang","year":"2016","journal-title":"Virus Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3390\/v9070177","article-title":"Porcine epidemic diarrhea in Europe: in-detail analyses of disease dynamics and molecular epidemiology","volume":"9","author":"Hanke","year":"2017","journal-title":"Viruses"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1099\/jgv.0.000419","article-title":"Pathogenesis comparison between the United States porcine epidemic diarrhoea virus prototype and S-INDEL-variant strains in conventional neonatal piglets","volume":"97","author":"Chen","year":"2016","journal-title":"J Gen Virol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.vetmic.2015.04.022","article-title":"Comparative pathogenesis of US porcine epidemic diarrhea virus (PEDV) strain PC21A in conventional 9\u2009days-old nursing piglets vs. 26\u2009days-old weaned pigs","volume":"178","author":"Jung","year":"2015","journal-title":"Vet Microbiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13567-015-0278-9","article-title":"Experimental infection of a US spike-insertion deletion porcine epidemic diarrhea virus in conventional nursing piglets and cross-protection to the original US PEDV infection","volume":"46","author":"Lin","year":"2015","journal-title":"Vet Res"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.rvsc.2015.09.024","article-title":"Isolation and experimental inoculation of an S INDEL strain of porcine epidemic diarrhea virus in Japan","volume":"103","author":"Yamamoto","year":"2015","journal-title":"Res Vet Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.3390\/v14122751","article-title":"Experimental infection of pigs with recent European porcine epidemic diarrhea viruses","volume":"14","author":"Lazov","year":"2022","journal-title":"Viruses"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.vetmic.2018.09.025","article-title":"Limited shedding of an S-InDel strain of porcine epidemic diarrhea virus (PEDV) in semen and questions regarding the infectivity of the detected virus","volume":"228","author":"Gallien","year":"2019","journal-title":"Vet Microbiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1111\/tbed.12509","article-title":"Experimental infection of young pigs with an early European strain of porcine epidemic diarrhoea virus and a recent US strain","volume":"64","author":"Lohse","year":"2017","journal-title":"Transbound Emerg Dis"},{"key":"ref16","first-page":"1320","article-title":"Characterization of the structural proteins of porcine epizootic diarrhea virus, strain CV777","volume":"49","author":"Egberink","year":"1988","journal-title":"Am J Vet Res"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1128\/JCM.02820-13","article-title":"Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States","volume":"52","author":"Chen","year":"2014","journal-title":"J Clin Microbiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0139266","DOI":"10.1371\/journal.pone.0139266","article-title":"Effect of porcine epidemic diarrhea virus infectious doses on infection outcomes in naive conventional neonatal and weaned pigs","volume":"10","author":"Thomas","year":"2015","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s13567-016-0402-5","article-title":"Increased frequency of porcine epidemic diarrhea virus shedding and lesions in suckling pigs compared to nursery pigs and protective immunity in nursery pigs after homologous re-challenge","volume":"47","author":"Gerber","year":"2016","journal-title":"Vet Res"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.tvjl.2014.07.018","article-title":"Detection of antibodies against porcine epidemic diarrhea virus in serum and colostrum by indirect ELISA","volume":"202","author":"Gerber","year":"2014","journal-title":"Vet J"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.mex.2015.10.001","article-title":"Detection of immunoglobulin (Ig) a antibodies against porcine epidemic diarrhea virus (PEDV) in fecal and serum samples","volume":"2","author":"Gerber","year":"2015","journal-title":"MethodsX"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1177\/1040638713501675","article-title":"Emergence of porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences","volume":"25","author":"Stevenson","year":"2013","journal-title":"J Vet Diagn Investig"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1177\/104063879901100512","article-title":"Monoclonal antibody-based immunohistochemical detection of porcine epidemic diarrhea virus antigen in formalin-fixed, paraffin-embedded intestinal tissues","volume":"11","author":"Kim","year":"1999","journal-title":"J Vet Diagn Investig"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"25961","DOI":"10.1038\/srep25961","article-title":"X-ray structure and inhibition of 3C-like protease from porcine epidemic diarrhea virus","volume":"6","author":"St John","year":"2016","journal-title":"Sci Rep"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"240","DOI":"10.3390\/v12020240","article-title":"Structural basis for inhibiting porcine epidemic diarrhea virus replication with the 3C-like protease inhibitor GC376","volume":"12","author":"Ye","year":"2020","journal-title":"Viruses"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1099\/0022-1317-74-9-1795","article-title":"Sequence determination of the nucleocapsid protein gene of the porcine epidemic diarrhea virus confirms that this virus is a coronavirus related to human coronavirus 229E and porcine transmissible gastroenteritis virus","volume":"74","author":"Bridgen","year":"1993","journal-title":"J Gen Virol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s0165-2427(01)00417-2","article-title":"Mucosal and systemic isotype-specific antibody responses and protection in conventional pigs exposed to virulent or attenuated porcine epidemic diarrhoea virus","volume":"85","author":"de Arriba","year":"2002","journal-title":"Vet Immunol Immunopathol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1177\/030098588201900108","article-title":"Pathology of experimental CV777 coronavirus enteritis in piglets. I. Histological and histochemical study","volume":"19","author":"Coussement","year":"1982","journal-title":"Vet Pathol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1016\/s0264-410x(99)00059-6","article-title":"Derivation of attenuated porcine epidemic diarrhea virus (PEDV) as vaccine candidate","volume":"17","author":"Kweon","year":"1999","journal-title":"Vaccine"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e01451","DOI":"10.1128\/mBio.01451-15","article-title":"Characterization of a pathogenic full-length cDNA clone and transmission model for porcine epidemic diarrhea virus strain PC22A","volume":"7","author":"Beall","year":"2016","journal-title":"mBio"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.virusres.2016.05.031","article-title":"Cellular entry of the porcine epidemic diarrhea virus","volume":"226","author":"Li","year":"2016","journal-title":"Virus Res"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/0378-1135(90)90154-N","article-title":"Intestinal replication of a porcine respiratory coronavirus closely related antigenically to the enteric transmissible gastroenteritis virus","volume":"23","author":"Cox","year":"1990","journal-title":"Vet Microbiol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1177\/0300985814522077","article-title":"Feline infectious peritonitis: still an enigma?","volume":"51","author":"Kipar","year":"2014","journal-title":"Vet Pathol"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2023.1279162\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T21:13:32Z","timestamp":1700428412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2023.1279162\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,16]]},"references-count":33,"alternative-id":["10.3389\/fvets.2023.1279162"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2023.1279162","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,16]]},"article-number":"1279162"}}