title: The vOTU domain of highly-pathogenic porcine reproductive and respiratory syndrome virus displays a differential substrate preference.
abstract: Arterivirus genus member Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically devastating disease, recently exacerbated by the emergence of highly pathogenic strains (HP-PRRSV). Within the nonstructural protein 2 of PRRSV is a deubiquitinating enzyme domain belonging to the viral ovarian tumor (vOTU) protease superfamily. vOTUs, which can greatly vary in their preference for their host ubiquitin (Ub) and Ub-like substrates such as interferon stimulated gene 15 (ISG15), have been implicated as a potential virulence factor. Since various strains of PRRSV have large variations in virulence, the specificity of vOTUs from two PRRSV strains of varying virulence were determined. While both vOTUs showed de-ubiquitinating activity and markedly low deISGylating activity, HP-PRRSV demonstrated a strong preference for lysine 63-linked poly-Ubiquitin, tied to innate immune response regulation. This represents the first report of biochemical activity unique to HP-PRRSV that has implications for a potential increase in immunosuppression and virulence.
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Deaton
authors.affiliation: Virus and Prion Research Unit, USDA-ARS-National Animal Disease Center, Ames, IA 50010, USA.
authors.forename: Allyn
authors.initials: A
authors.lastname: Spear
authors.affiliation: Virus and Prion Research Unit, USDA-ARS-National Animal Disease Center, Ames, IA 50010, USA.
authors.forename: Kay S
authors.initials: KS
authors.lastname: Faaberg
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA. Electronic address: spegan@uga.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Pegan
mesh_terms: D000818:Animals; D019316:Porcine respiratory and reproductive syndrome virus / Q000201:enzymology* / Q000302:isolation & purification; D013379:Substrate Specificity; D013552:Swine; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; D064570:Ubiquitin-Specific Proteases
keywords: ISG15; PLP2; PRRSV; Ubiquitin; nsp2; vOTU
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