title: Functional analysis of the porcine USP18 and its role during porcine arterivirus replication.
abstract: Emerging evidence places deubiquitylation at the core of a multitude of regulatory processes, ranging from cell growth to innate immune response and health, such as cancer, degenerative and infectious diseases. Little is known about deubiquitylation in pig and arterivirus infection. This report provides information on the biochemical and functional role of the porcine USP18 during innate immune response to the porcine respiratory and reproductive syndrome virus (PRRSV). We have shown that UBP gene is the ortholog of the murine USP18 (Ubp43) gene and the human ubiquitin specific protease 18 (USP18) gene and encodes a biochemically functional de-ubiquitin enzyme which inhibits signalling pathways that lead to IFN-stimulating response element (ISRE) promotor regulation. Furthermore we have demonstrated that overexpression of the porcine USP18 leads to reduced replication and/or growth of PRRSV. Our data contrast with the conclusion of numerous reports demonstrating that USP18-deficient mice are highly resistant to viral and bacterial infections and to oncogenic transformation by BCR-ABL, and highlight USP18 as a potential target gene that promotes reduced replication of PRRSV.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PS, UK. tahar.aitali@roslin.ed.ac.uk
authors.forename: Tahar
authors.initials: T
authors.lastname: Ait-Ali
authors.forename: Alison W
authors.initials: AW
authors.lastname: Wilson
authors.forename: Heather
authors.initials: H
authors.lastname: Finlayson
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Carré
authors.forename: Sreenivasa Chakravarthy
authors.initials: SC
authors.lastname: Ramaiahgari
authors.forename: David G
authors.initials: DG
authors.lastname: Westcott
authors.forename: Martin
authors.initials: M
authors.lastname: Waterfall
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Frossard
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Drew
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bishop
authors.forename: Alan L
authors.initials: AL
authors.lastname: Archibald
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D010450:Endopeptidases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D011401:Promoter Regions, Genetic; D034421:Sus scrofa; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination; D014779:Virus Replication
chemical_list: D010450:Endopeptidases; C118306:Usp18 protein, mouse; C485560:USP18 protein, human; D043222:Ubiquitin Thiolesterase