{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:24:37Z","timestamp":1777512277314,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32122086"],"award-info":[{"award-number":["32122086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["#61626817"],"award-info":[{"award-number":["#61626817"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["32122086"],"award-info":[{"award-number":["32122086"]}]},{"name":"National Key Research and Development Program of China","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}]},{"name":"National Key Research and Development Program of China","award":["#61626817"],"award-info":[{"award-number":["#61626817"]}]},{"name":"Walmart Foundation as well as Walmart Food Safety Collaboration Center","award":["32122086"],"award-info":[{"award-number":["32122086"]}]},{"name":"Walmart Foundation as well as Walmart Food Safety Collaboration Center","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}]},{"name":"Walmart Foundation as well as Walmart Food Safety Collaboration Center","award":["#61626817"],"award-info":[{"award-number":["#61626817"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Pseudorabies virus (PRV) generally infects pigs and threatens the pig industry. However, recently we have isolated a PRV strain designated hSD-1\/2019 from infected humans. In this study, we compared the complete genome sequence of hSD-1\/2019 with those of pig-originated PRV strains. Sequence alignments revealed that the genome sequence of hSD-1\/2019 was highly homologous to those of the porcine PRV strains. Phylogenetic analyses found that hSD-1\/2019 was the closest related to porcine PRV endemic strains in China, particularly the variant strains circulating recently. We also showed that the glycoproteins important for the multiplication and pathogenesis of hSD-1\/2019 were highly similar to those of the pig endemic strains. Diversifying selection analyses revealed that hSD-1\/2019 and pig variant strains are under diversifying selection. Recombination analysis indicated that hSD-1\/2019 was a recombinant of several PRV variant strains and an earlier PRV classic strain. Finally, we found that both human and pig-originated PRV strains could induce cytopathic effects in cells from humans, pigs, and mice, but only the human PRV and pig-variant PRV formed large syncytia in human cell lines. The data presented in this study contribute to our understanding of the molecular basis for the pathogenesis of human PRV from a genomic aspect.<\/jats:p>","DOI":"10.3390\/v15010170","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T01:48:19Z","timestamp":1672969699000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cytopathic and Genomic Characteristics of a Human-Originated Pseudorabies Virus"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-328X","authenticated-orcid":false,"given":"Zhong","family":"Peng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig 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China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibo","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-386X","authenticated-orcid":false,"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive 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Ministry of Agriculture of China, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-1378","authenticated-orcid":false,"given":"Xiangru","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of China, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry 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Prev. Med. Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1098\/rstb.2001.0888","article-title":"Risk factors for human disease emergence","volume":"356","author":"Taylor","year":"2001","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_3","first-page":"99","article-title":"Aujeszky\u2019s disease (pseudorabies) virus: The virus and molecular pathogenesis-state of the art, June 1999","volume":"31","author":"Mettenleiter","year":"2000","journal-title":"Vet. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1128\/MMBR.69.3.462-500.2005","article-title":"Molecular biology of pseudorabies virus: Impact on neurovirology and veterinary medicine","volume":"69","author":"Pomeranz","year":"2005","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.virol.2015.04.013","article-title":"Genomic characterization of emergent pseudorabies virus in China reveals marked sequence divergence: Evidence for the existence of two major genotypes","volume":"483","author":"Ye","year":"2015","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e5785","DOI":"10.7717\/peerj.5785","article-title":"Epidemiological and genetic characteristics of swine pseudorabies virus in mainland China between 2012 and 2017","volume":"6","author":"Sun","year":"2018","journal-title":"PeerJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1080\/22221751.2018.1563459","article-title":"Pseudorabies virus: A neglected zoonotic pathogen in humans?","volume":"8","author":"Wong","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.jinf.2019.12.018","article-title":"Human pseudorabies virus infection: A new threat in China","volume":"80","author":"Ou","year":"2020","journal-title":"J. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.3201\/eid1911.130177","article-title":"Pseudorabies virus variant in Bartha-K61-vaccinated pigs, China, 2012","volume":"19","author":"An","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.vetmic.2014.09.003","article-title":"Pathogenicity and genomic characterization of a pseudorabies virus variant isolated from Bartha-K61-vaccinated swine population in China","volume":"174","author":"Luo","year":"2014","journal-title":"Vet. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3201\/eid2406.171612","article-title":"Human Endophthalmitis Caused By Pseudorabies Virus Infection, China, 2017","volume":"24","author":"Ai","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s13365-019-00822-2","article-title":"Human encephalitis caused by pseudorabies virus infection: A case report","volume":"26","author":"Wang","year":"2020","journal-title":"J. Neurovirol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ijid.2019.09.019","article-title":"Human encephalitis complicated with bilateral acute retinal necrosis associated with pseudorabies virus infection: A case report","volume":"89","author":"Wang","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3389\/fneur.2019.00534","article-title":"A Case of Human Viral Encephalitis Caused by Pseudorabies Virus Infection in China","volume":"10","author":"Yang","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ijid.2019.08.007","article-title":"Characteristics of human encephalitis caused by pseudorabies virus: A case series study","volume":"87","author":"Yang","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_16","first-page":"1152","article-title":"Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus","volume":"98","author":"Zhao","year":"2018","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1111\/tbed.13297","article-title":"Dynamic cerebrospinal fluid analyses of severe pseudorabies encephalitis","volume":"66","author":"Zheng","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1093\/cid\/ciaa987","article-title":"A novel human acute encephalitis caused by pseudorabies virus variant strain","volume":"73","author":"Liu","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","first-page":"3151","article-title":"Preparation of viral DNA from nucleocapsids","volume":"10","author":"Szpara","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1186\/1756-0500-5-337","article-title":"AdapterRemoval: Easy cleaning of next-generation sequencing reads","volume":"5","author":"Lindgreen","year":"2012","journal-title":"BMC Res. Notes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/2047-217X-1-18","article-title":"SOAPdenovo2: An empirically improved memory-efficient short-read de novo assembler","volume":"1","author":"Luo","year":"2012","journal-title":"GigaScience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1093\/bioinformatics\/btu661","article-title":"A5-miseq: An updated pipeline to assemble microbial genomes from Illumina MiSeq data","volume":"31","author":"Coil","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1101\/gr.215087.116","article-title":"Canu: Scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation","volume":"27","author":"Koren","year":"2017","journal-title":"Genome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e112963","DOI":"10.1371\/journal.pone.0112963","article-title":"Pilon: An integrated tool for comprehensive microbial variant detection and genome assembly improvement","volume":"9","author":"Walker","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/bioinformatics\/btr039","article-title":"Easyfig: A genome comparison visualizer","volume":"27","author":"Sullivan","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_27","first-page":"5","article-title":"MAFFT-DASH: Integrated protein sequence and structural alignment","volume":"47","author":"Rozewicki","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1099\/ijs.0.64483-0","article-title":"DNA-DNA hybridization values and their relationship to whole-genome sequence similarities","volume":"57","author":"Goris","year":"2007","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1006650","DOI":"10.1371\/journal.pcbi.1006650","article-title":"BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis","volume":"15","author":"Bouckaert","year":"2019","journal-title":"PLoS Comput. Biol."},{"key":"ref_30","first-page":"145","article-title":"Assessing the applicability of the GTR nucleotide substitution model through simulations","volume":"2","author":"Gatto","year":"2007","journal-title":"Evol. Bioinform."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"W256","DOI":"10.1093\/nar\/gkz239","article-title":"Interactive Tree Of Life (iTOL) v4: Recent updates and new developments","volume":"47","author":"Letunic","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/gb-2004-5-2-r12","article-title":"Versatile and open software for comparing large genomes","volume":"5","author":"Kurtz","year":"2004","journal-title":"Genome Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.gene.2016.01.041","article-title":"Genomic characterization of Pasteurella multocida HB01, a serotype A bovine isolate from China","volume":"581","author":"Peng","year":"2016","journal-title":"Gene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"003","DOI":"10.1093\/ve\/vev003","article-title":"RDP4: Detection and analysis of recombination patterns in virus genomes","volume":"1","author":"Martin","year":"2015","journal-title":"Virus Evol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12985-020-01387-x","article-title":"Whole genomic analysis of a potential recombinant human adenovirus type 1 in Qinghai plateau, China","volume":"17","author":"Yu","year":"2020","journal-title":"Virol. J."},{"key":"ref_36","first-page":"501","article-title":"Pseudorabies in man","volume":"1","author":"Mravak","year":"1987","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s12250-019-00140-1","article-title":"Genome Characteristics and Evolution of Pseudorabies Virus Strains in Eastern China from 2017 to 2019","volume":"34","author":"Zhai","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.1016\/j.vaccine.2015.09.066","article-title":"Novel pseudorabies virus variant with defects in TK, gE and gI protects growing pigs against lethal challenge","volume":"33","author":"Hu","year":"2015","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e1006314","DOI":"10.1371\/journal.ppat.1006314","article-title":"Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D","volume":"13","author":"Li","year":"2017","journal-title":"PLoS Pathog."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/ncomms1571","article-title":"Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion","volume":"2","author":"Zhang","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jtbi.2005.08.037","article-title":"Comparisons of dN\/dS are time dependent for closely related bacterial genomes","volume":"239","author":"Rocha","year":"2006","journal-title":"J. Theor. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.virol.2016.01.016","article-title":"Genomic analyses reveal that partial sequence of an earlier pseudorabies virus in China is originated from a Bartha-vaccine-like strain","volume":"491","author":"Ye","year":"2016","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1051\/vetres:200661","article-title":"Cell biological and molecular characteristics of pseudorabies virus infections in cell cultures and in pigs with emphasis on the respiratory tract","volume":"38","author":"Nauwynck","year":"2007","journal-title":"Vet. Res."},{"key":"ref_44","unstructured":"Saito, A., Nasser, H., Uriu, K., Kosugi, Y., Irie, T., Shirakawa, K., Sadamasu, K., Kimura, I., Ito, J., and Wu, J. (2021). SARS-CoV-2 spike P681R mutation enhances and accelerates viral fusion. bioRxiv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6760","DOI":"10.1128\/JVI.74.15.6760-6768.2000","article-title":"Pseudorabies virus glycoprotein M inhibits membrane fusion","volume":"74","author":"Klupp","year":"2000","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6845","DOI":"10.1128\/JVI.76.13.6845-6851.2002","article-title":"A tyrosine-based motif in the cytoplasmic tail of pseudorabies virus glycoprotein B is important for both antibody-induced internalization of viral glycoproteins and efficient cell-to-cell spread","volume":"76","author":"Favoreel","year":"2002","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1128\/jvi.66.4.2316-2325.1992","article-title":"Glycoprotein gI of pseudorabies virus promotes cell fusion and virus spread via direct cell-to-cell transmission","volume":"66","author":"Zsak","year":"1992","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12985-020-01312-2","article-title":"Isobavachalcone inhibits Pseudorabies virus by impairing virus-induced cell-to-cell fusion","volume":"17","author":"Wang","year":"2020","journal-title":"Virol. J."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/1\/170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:00:36Z","timestamp":1760119236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/1\/170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["v15010170"],"URL":"https:\/\/doi.org\/10.3390\/v15010170","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]}}}