{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:46:48Z","timestamp":1760150808155,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Pseudorabies virus (PRV) is the causative agent for Aujeszky\u2019s disease, a disease that mainly affects pigs and incidentally other domestic and wild animals. While PRV is almost always fatal, causing neurological disease independently of the age in non-porcine species, the development of neurological manifestation in its host species, the pig, highly depends on the age. In this study, an attempt was made to investigate the effect of nerve development on the outcome of virus infection and the effect of virus infection on the structure of nerves in piglets of various ages. For that reason, 42 pigs at the age of one (n = 14), three (n = 14) and five (n = 14) weeks were inoculated with 107 TCID50 of PRV Kaplan strain and euthanized at one- or four-days post inoculation (DPI). The tissues of the trigeminal nervous pathway were collected and examined for virus replication (titration) in cell cultures for nerve morphology by light and transmission electron microscopy, and for viral antigen visualization by immunohistochemistry. The results showed that as the age of the pig increases, virus titers and clinical manifestations reduced, while, at the same time, myelin and axon development ceased. Following infection, the nerve structure was disrupted at all ages examined, being more prominent in one-week-old pigs compared to five-week-old pigs. In conclusion, the age-dependent PRV neuroinvasion in pigs seems to correlate with the morphological changes of neurons.<\/jats:p>","DOI":"10.3390\/pathogens11020157","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T04:49:51Z","timestamp":1643258991000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Age-Dependent Invasion of Pseudorabies Virus into Porcine Central Nervous System via Maxillary Nerve"],"prefix":"10.3390","volume":"11","author":[{"given":"Konstantinos","family":"Papageorgiou","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-4398","authenticated-orcid":false,"given":"Ioannis","family":"Grivas","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Chiotelli","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8524-6218","authenticated-orcid":false,"given":"Alexandros","family":"Theodoridis","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Production Economics, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-6078","authenticated-orcid":false,"given":"Emmanuel","family":"Panteris","sequence":"additional","affiliation":[{"name":"Department of Botany, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-9280","authenticated-orcid":false,"given":"Dimitris","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3532-5724","authenticated-orcid":false,"given":"Evanthia","family":"Petridou","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Papaioannou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-0713","authenticated-orcid":false,"given":"Hans","family":"Nauwynck","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-9928","authenticated-orcid":false,"given":"Spyridon K.","family":"Kritas","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","first-page":"99","article-title":"Aujeszky\u2019s disease (pseudorabies) virus: The virus and molecular pathogenesis\u2014State of the art, June 1999","volume":"31","author":"Mettenleiter","year":"2000","journal-title":"Vet. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.vetmic.2009.06.020","article-title":"Herpesviruses\u2014A zoonotic threat?","volume":"140","author":"Tischer","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_3","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_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.vetmic.2010.02.013","article-title":"Variation of Aujeszky\u2019s disease viruses in wild swine in USA","volume":"143","author":"Hahn","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1751-0813.2000.tb11862.x","article-title":"Aujeszky\u2019s disease eradication in New Zealand","volume":"78","author":"MacDiarmid","year":"2000","journal-title":"Aust. Vet. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1046\/j.1439-0450.2003.00666.x","article-title":"Eradication of Aujeszky\u2019s disease in Germany","volume":"50","author":"Muller","year":"2003","journal-title":"J. Vet. Med. B Infect. Dis. Vet. Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1098\/rstb.2009.0086","article-title":"Wild boars as sources for infectious diseases in livestock and humans","volume":"364","author":"Meng","year":"2009","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_10","first-page":"27","article-title":"Pseudorabies virus infection (Aujeszky\u2019s disease) in wild swine","volume":"2","author":"Muller","year":"2000","journal-title":"Infect. Dis. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1007\/s00705-011-1080-2","article-title":"Pseudorabies virus in wild swine: A global perspective","volume":"156","author":"Muller","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tvjl.2007.02.017","article-title":"A review of viral diseases of the European wild boar: Effects of population dynamics and reservoir role","volume":"176","author":"Segales","year":"2008","journal-title":"Vet. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3390\/v5020678","article-title":"Directional Spread of Alphaherpesviruses in the Nervous System","volume":"5","author":"Kramer","year":"2013","journal-title":"Viruses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1099\/0022-1317-75-9-2319","article-title":"Role of Envelope Glycoproteins gI, gp63 and gIII in the Invasion and Spread of Aujezky\u2019s Disease virus in the Olfactory Nervous Pathway of the Pig","volume":"75","author":"Kritas","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_15","first-page":"309","article-title":"Role of gp63 and gp III of Aujeszky\u2019s Disease Virus in the Invasion of the Olfactory Nervous Pathway in Neonatal Pigs","volume":"42","author":"Kritas","year":"1994","journal-title":"Acta Vet. Hung."},{"key":"ref_16","unstructured":"Kritas, S. (1994). Neuropathogenesis of Wild-Type and Deleted Aujeszky\u2019s Disease Virus Strains in Pigs with and without Specific Maternal Antibodies. [Ph.D. Thesis, University of Gent]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0378-1135(94)90120-1","article-title":"Invasion and spread of single glycoprotein deleted mutants of Aujeszky\u2019s disease virus (ADV) in the trigeminal nervous pathway of pigs after intranasal inoculation","volume":"40","author":"Kritas","year":"1994","journal-title":"Vet. Microbiol."},{"key":"ref_18","unstructured":"Mettenleiter, T.C., Ehlers, B., Muller, T., Yoon, K.-J., and Teifke, J.P. (2012). Herpesviruses. Diseases of Swine, Wiley-Blackwell. [10th ed.]."},{"key":"ref_19","first-page":"12234","article-title":"Myelin Sheath Development in the Maxillary Nerve of the Newborn Pig","volume":"11","author":"Papageorgiou","year":"2016","journal-title":"Anat. Histol. Embryol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1083\/jcb.200510156","article-title":"\u03b1-Herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites","volume":"174","author":"Nauwynck","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0006-8993(01)02241-7","article-title":"Two paths for dissemination of herpes simplex virus from infected trigeminal ganglion to the murine cornea","volume":"899","author":"Ohara","year":"2001","journal-title":"Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8310","DOI":"10.1128\/JVI.76.16.8310-8317.2002","article-title":"In vivo egress of an alphaherpesvirus from axons","volume":"76","author":"Tomishima","year":"2002","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jneumeth.2017.06.005","article-title":"Simple and reproducible approaches for the collection of select porcine ganglia","volume":"289","author":"Meyerholz","year":"2017","journal-title":"J. Neurosci. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1385-299X(01)00064-2","article-title":"How to use the optical fractionator: An example based on the estimation of neurons in the hippocampal CA1 and CA3 regions of tree shrews","volume":"7","author":"Keuker","year":"2001","journal-title":"Brain Res. Protoc."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:08:02Z","timestamp":1760134082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["pathogens11020157"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11020157","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2022,1,26]]}}}