title: Rescue of wild-type mumps virus from a strain associated with recent outbreaks helps to define the role of the SH ORF in the pathogenesis of mumps virus.
abstract: Mumps virus (MuV) causes acute infections in humans. In recent years, MuV has caused epidemics among highly vaccinated populations. The largest outbreak in the U.S. in the past 20 years occurred in 2005-2006 with over 5000 reported cases in which the majority of the cases was in vaccinated young adults. We sequenced the complete genome of a representative strain from the epidemic (MuV-IA). MuV-IA is a member of genotype G, the same genotype of MuV that was associated with the outbreak in the UK in 2004-2005. We constructed a reverse genetics system for MuV-IA (rMuV-IA), and rescued a virus lacking the open reading frame (ORF) of the SH gene (rMuV∆SH). rMuV∆SH infection in L929 cells induced increased NF-κB activation, TNF-α production and apoptosis compared to rMuV-IA. rMuV∆SH was attenuated in an animal model. These results indicated that the SH ORF of MuV plays a significant role in interfering with TNF-α signaling and viral pathogenesis during virus infection.
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, GA 30602, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Dengyun
authors.initials: D
authors.lastname: Sun
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rota
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D004196:Disease Outbreaks; D004797:Enzyme-Linked Immunosorbent Assay; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D016679:Genome, Viral; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D009107:Mumps / Q000453:epidemiology / Q000821:virology*; D009109:Mumps virus / Q000235:genetics* / Q000472:pathogenicity; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames / Q000502:physiology*; D010802:Phylogeny; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology; D014481:United States / Q000453:epidemiology; D014709:Vero Cells
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha