{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:17:51Z","timestamp":1794028671075,"version":"4.8.0"},"reference-count":29,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program of the Ningxia Hui Autonomous Region","award":["(#2021BEF02028)"],"award-info":[{"award-number":["(#2021BEF02028)"]}]},{"name":"Key Research and Development Program of the Ningxia Hui Autonomous Region","award":["(CARS-37)"],"award-info":[{"award-number":["(CARS-37)"]}]},{"name":"Chinese Agricultural Research System of MOF and MARA","award":["(#2021BEF02028)"],"award-info":[{"award-number":["(#2021BEF02028)"]}]},{"name":"Chinese Agricultural Research System of MOF and MARA","award":["(CARS-37)"],"award-info":[{"award-number":["(CARS-37)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Infectious bovine rhinotracheitis (IBR) caused by bovine herpes virus 1 (BoHV-1) can lead to enormous economic losses in the cattle industry. Vaccine immunization is preferentially used to decrease its transmission speed and resultant clinical signs, rather than to completely stop viral infection. Therefore, a drug effective in treating IBR is urgently needed. Our previous work demonstrated that ivermectin significantly inhibited viral replication in a cell infection model. This study aimed to investigate its antiviral effects in vivo by using a rabbit infection model. The viral inhibition assay was first used to confirm that ivermectin at low concentrations (6\u201325 nM) could reduce viral titers (TCID50) significantly (p &lt; 0.001) at 24 h post-infection. In rabbits, ivermectin was administrated with one to three doses, based on the recommended anti-parasite treatment dosage (0.2 mg\/kg bodyweight) through subcutaneous injection at different days post-infection in the treated IBRV infection groups, while non-treated infection group was used as the control. The infected rabbits showed hyperthermia and other clinical signs, but the number of high-fever rabbits in the ivermectin treatment groups was significantly lower than that in the non-treated infection group. Furthermore, in ivermectin treatment groups, the cumulative clinical scores correlated negatively with drug doses and positively with delay of administration time post-infection. The overall nasal shedding time in ivermectin-treated groups was two days shorter than the non-treated challenge group. At the same time point, the titer of neutralizing antibodies in the treatment group with triple doses was higher than the other two-dose groups, but the difference between the treatment groups decreased with the delay of drug administration. Correspondingly, the serious extent of lung lesions was negatively related to the dosage, but positively related to the delay of drug administration. The qPCR with tissue homogenates showed that the virus was present in both the lung tissues and trigeminals of the infected rabbits. In conclusion, ivermectin treatment had therapeutic effect by decreasing clinical signs and viral shedding, but could not stop virus proliferation in lung tissues and trigeminals.<\/jats:p>","DOI":"10.3390\/ani13203164","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T10:23:42Z","timestamp":1696933422000},"page":"3164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of Antiviral Activity of Ivermectin against Infectious Bovine Rhinotracheitis Virus in Rabbit Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Chen","family":"Wang","sequence":"first","affiliation":[{"name":"The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ruminant Bio-Products, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1200-5314","authenticated-orcid":false,"given":"Yingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ruminant Bio-Products, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ruminant Bio-Products, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changmin","family":"Hu","sequence":"additional","affiliation":[{"name":"The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ruminant Bio-Products, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Chen","sequence":"additional","affiliation":[{"name":"The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ruminant Bio-Products, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhen","family":"Guo","sequence":"additional","affiliation":[{"name":"The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ruminant Bio-Products, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","unstructured":"Wyler, R., Engels, M., and Schwyzer, M. (1989). Herpesvirus Diseases of Cattle, Horses, and Pigs, Springer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/tbed.13718","article-title":"MAN alpha 1-2MAN decorated liposomes enhance the immunogenicity induced by a DNA vaccine against BoHV-1","volume":"68","author":"Kornuta","year":"2021","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.1016\/j.vaccine.2014.07.004","article-title":"A triple gene mutant of BoHV-1 administered intranasally is significantly more efficacious than a BoHV-1 glycoprotein E-deleted virus against a virulent BoHV-1 challenge","volume":"32","author":"Chowdhury","year":"2014","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1600-065X.2011.01074.x","article-title":"Immune modulation during latent herpesvirus infection","volume":"245","author":"White","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_5","first-page":"72","article-title":"Bovine herpesvims 1 productive infection stimulates inflammasome formation and caspase 1 activity","volume":"185","author":"Wiebe","year":"2014","journal-title":"Virus Res. Int. J. Mol. Cell. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.vaccine.2020.11.071","article-title":"A plasmid encoding the extracellular domain of CD40 ligand and Montanide GEL01 as adjuvants enhance the immunogenicity and the protection induced by a DNA vaccine against BoHV-1\u2014ScienceDirect","volume":"39","author":"Caka","year":"2021","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.antiviral.2018.09.010","article-title":"Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo","volume":"159","author":"Lv","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Raza, S., Shahin, F., Zhai, W., Li, H., and Guo, A. (2020). Ivermectin Inhibits Bovine Herpesvirus 1 DNA Polymerase Nuclear Import and Interferes With Viral Replication. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030409"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Formiga, F.R., Leblanc, R., Rebouas, J.D.S., Farias, L.P., Oliveira, R.N.D., and Pena, L. (2021). Ivermectin: An Award-Winning Drug with Expected Antiviral Activity against COVID-19, Elsevier.","DOI":"10.1016\/j.jconrel.2020.10.009"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/cpt.1889","article-title":"The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19","volume":"108","author":"Schmith","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1046\/j.1365-2885.1997.00825.x","article-title":"Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle","volume":"20","author":"Lanusse","year":"1997","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jviromet.2008.03.008","article-title":"A simple method of infecting rabbits with Bovine herpesvirus 1 and 5","volume":"150","author":"Valera","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s12250-013-3283-z","article-title":"An inactivated vaccine from a field strain of bovine herpesvirus-1 (BoHV-1) has high antigenic mass and induces strong efficacy in a rabbit model","volume":"28","author":"Jairo","year":"2013","journal-title":"Virol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1089\/vim.2011.0018","article-title":"Recombinant MVA expressing secreted glycoprotein D of BoHV-1 induces systemic and mucosal immunity in animal models","volume":"24","author":"Ferrer","year":"2011","journal-title":"Viral Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.rvsc.2013.03.017","article-title":"Systemic infection induced by intranasal inoculation of Bovine herpesvirus 1.1 in pregnant and non-pregnant rabbits","volume":"95","author":"Valera","year":"2013","journal-title":"Res. Vet. Ence"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1080\/13550280701375433","article-title":"Envelope protein Us9 is required for the anterograde transport of bovine herpesvirus type 1 from trigeminal ganglia to nose and eye upon reactivation","volume":"13","author":"Butchi","year":"2007","journal-title":"J. Neurovirology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41429-020-0336-z","article-title":"Ivermectin: A systematic review from antiviral effects to COVID-19 complementary regimen","volume":"73","author":"Heidary","year":"2020","journal-title":"J. Antibiot."},{"key":"ref_18","unstructured":"Deng, M. (2015). Investigation of Gene Deleted Vaccine of Infectious Bovine Rhinotracheitis Virus and Its Application. [Ph.D. Thesis, Hua Zhong Agriculture University]."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104914","DOI":"10.1016\/j.micpath.2021.104914","article-title":"Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1","volume":"155","author":"Naeem","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00705-015-2653-2","article-title":"Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine alveolar macrophages","volume":"161","author":"Lee","year":"2016","journal-title":"Arch. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"198384","DOI":"10.1016\/j.virusres.2021.198384","article-title":"Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro","volume":"297","author":"Yesilbag","year":"2021","journal-title":"Virus Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1042\/BJ20120150","article-title":"Ivermectin is a specific inhibitor of importin alpha\/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus","volume":"443","author":"Wagstaff","year":"2012","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1046\/j.1365-2885.2003.00526.x","article-title":"The comparative serum disposition kinetics of subcutaneous administration of doramectin, ivermectin and moxidectin in the Australian Merino sheep","volume":"26","author":"Barber","year":"2010","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1258\/la.2009.009053","article-title":"Plasma dispositions of ivermectin, doramectin and moxidectin following subcutaneous administration in rabbits","volume":"44","author":"Gokbulut","year":"2010","journal-title":"Lab. Anim."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ar\u00e9valo, A., Pagotto, R., P\u00f3rfido, J., Daghero, H., and Crispo, M. (2020). Ivermectin Reduces Coronavirus Infection In Vivo: A Mouse Experimental Model, Cold Spring Harbor Laboratory.","DOI":"10.1101\/2020.11.02.363242"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41429-023-00623-0","article-title":"Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model","volume":"76","author":"Uematsu","year":"2023","journal-title":"J. Antibiot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"462","DOI":"10.18433\/jpps31457","article-title":"Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis: Ivermectin in COVID-19: A meta-analysis","volume":"23","author":"Padhy","year":"2020","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0378-1135(01)00498-9","article-title":"Analysis of bovine trigeminal ganglia following infection with bovine herpesvirus 1","volume":"86","author":"Winkler","year":"2002","journal-title":"Vet. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1128\/JVI.74.11.5337-5346.2000","article-title":"Persistence and Reactivation of Bovine Herpesvirus 1 in the Tonsils of Latently Infected Calves","volume":"74","author":"Winkler","year":"2000","journal-title":"J. Virol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/20\/3164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:21Z","timestamp":1760130261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/20\/3164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,10]]},"references-count":29,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ani13203164"],"URL":"https:\/\/doi.org\/10.3390\/ani13203164","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,10]]}}}