PMID- 25975520 OWN - NLM STAT- MEDLINE DCOM- 20160212 LR - 20201209 IS - 1873-2542 (Electronic) IS - 0378-1135 (Print) IS - 0378-1135 (Linking) VI - 178 IP - 1-2 DP - 2015 Jul 9 TI - In vivo assessment of equine arteritis virus vaccine improvement by disabling the deubiquitinase activity of papain-like protease 2. PG - 132-7 LID - S0378-1135(15)00163-7 [pii] LID - 10.1016/j.vetmic.2015.04.018 [doi] AB - Arteriviruses are a family of positive-stranded RNA viruses that includes the prototypic equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV). Although several vaccines against these viruses are commercially available there is room for improvement, especially in the case of PRRSV. The ability of arteriviruses to counteract the immune response is thought to decrease the efficacy of the current modified live virus vaccines. We have recently shown that the deubiquitinase (DUB) activity of EAV papain-like protease 2 (PLP2) is important for the inhibition of innate immune activation during infection. A vaccine virus lacking PLP2 DUB activity may therefore be more immunogenic and provide improved protection against subsequent challenge than its DUB-competent counterpart. To test this hypothesis, twenty Shetland mares were randomly assigned to one of three groups. Two groups were vaccinated, either with DUB-positive (n=9) or DUB-negative (n=9) recombinant EAV. The third group (n=2) was not vaccinated. All horses were subsequently challenged with the virulent KY84 strain of EAV. Both vaccine viruses proved to be replication competent in vivo. In addition, the DUB-negative virus provided a similar degree of protection against clinical disease as its DUB-positive parental counterpart. Owing to the already high level of protection provided by the parental virus, a possible improvement due to inactivation of PLP2 DUB activity could not be detected under these experimental conditions. Taken together, the data obtained in this study warrant further in vivo investigations into the potential of using DUB-mutant viruses for the improvement of arterivirus vaccines. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - van Kasteren, Puck B AU - van Kasteren PB AD - Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. FAU - Knaap, Robert C M AU - Knaap RC AD - Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. FAU - van den Elzen, Paul AU - van den Elzen P AD - MSD Animal Health, Wim de Korverstraat 35, 5831 AN Boxmeer, The Netherlands. FAU - Snijder, Eric J AU - Snijder EJ AD - Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. FAU - Balasuriya, Udeni B R AU - Balasuriya UB AD - Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, 1400 Nicholasville Road, 40546-0099 Lexington, KY, USA. FAU - van den Born, Erwin AU - van den Born E AD - MSD Animal Health, Wim de Korverstraat 35, 5831 AN Boxmeer, The Netherlands. FAU - Kikkert, Marjolein AU - Kikkert M AD - Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: m.kikkert@lumc.nl. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150430 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (Vaccines, Attenuated) RN - 0 (Viral Vaccines) RN - EC 3.4.19.12 (Ubiquitin-Specific Proteases) RN - EC 3.4.22.2 (Coronavirus Papain-Like Proteases) RN - EC 3.4.22.2 (Papain) SB - IM MH - Animals MH - Arterivirus Infections/prevention & control/*veterinary MH - Coronavirus Papain-Like Proteases MH - Equartevirus/*enzymology/immunology MH - Female MH - Horse Diseases/*prevention & control/*virology MH - Horses MH - Papain/*genetics MH - Treatment Outcome MH - Ubiquitin-Specific Proteases/*genetics MH - Vaccines, Attenuated/immunology/therapeutic use MH - Viral Vaccines/immunology/therapeutic use PMC - PMC7117436 OTO - NOTNLM OT - Arterivirus OT - Deubiquitinase OT - EAV OT - Interferon OT - PRRSV OT - Vaccine EDAT- 2015/05/16 06:00 MHDA- 2016/02/13 06:00 PMCR- 2015/04/30 CRDT- 2015/05/16 06:00 PHST- 2014/12/02 00:00 [received] PHST- 2015/04/03 00:00 [revised] PHST- 2015/04/20 00:00 [accepted] PHST- 2015/05/16 06:00 [entrez] PHST- 2015/05/16 06:00 [pubmed] PHST- 2016/02/13 06:00 [medline] PHST- 2015/04/30 00:00 [pmc-release] AID - S0378-1135(15)00163-7 [pii] AID - 10.1016/j.vetmic.2015.04.018 [doi] PST - ppublish SO - Vet Microbiol. 2015 Jul 9;178(1-2):132-7. doi: 10.1016/j.vetmic.2015.04.018. Epub 2015 Apr 30.