title: The V protein of mumps virus plays a critical role in pathogenesis.
abstract: Mumps virus (MuV) causes an acute infection in humans characterized by a wide array of symptoms ranging from relatively mild manifestations, such as parotitis, to more-severe complications, such as meningitis and encephalitis. Widespread mumps vaccination has reduced mumps incidence dramatically; however, outbreaks still occur in vaccinated populations. The V protein of MuV, when expressed in cell culture, blocks interferon (IFN) expression and signaling and interleukin-6 (IL-6) signaling. In this work, we generated a recombinant MuV incapable of expressing the V protein (rMuVΔV). The rescued MuV was derived from a clinical wild-type isolate from a recent outbreak in the United States (MuV(Iowa/US/06), G genotype). Analysis of the virus confirmed the roles of V protein in blocking IFN expression and signaling and IL-6 signaling. We also found that the rMuV(Iowa/US/06)ΔV virus induced high levels of IL-6 expression in vitro, suggesting that V plays a role in reducing IL-6 expression. In vivo, the rMuV(Iowa/US/06)ΔV virus was highly attenuated, indicating that the V protein plays an essential role in viral virulence.
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.forename: Priya
authors.initials: P
authors.lastname: Luthra
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Sandra
authors.initials: S
authors.lastname: Fuentes
authors.forename: James Alexander
authors.initials: JA
authors.lastname: D'Andrea
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.forename: Steven
authors.initials: S
authors.lastname: Rubin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rota
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D009109:Mumps virus / Q000378:metabolism / Q000472:pathogenicity*; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D014764:Viral Proteins
references.citation: J Virol. 2009 Jul;83(14):7252-60
references.pmid: 19403670
references.citation: J Virol. 2005 Apr;79(7):4451-9
references.pmid: 15767445
references.citation: J Virol. 1999 Aug;73(8):6228-34
references.pmid: 10400712
references.citation: J Med Virol. 2009 Oct;81(10):1819-25
references.pmid: 19697404
references.citation: Biochem Biophys Res Commun. 2001 Apr 27;283(1):255-9
references.pmid: 11322797
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2118-23
references.pmid: 21245317
references.citation: MMWR Morb Mortal Wkly Rep. 2006 Feb 24;55(7):173-5
references.pmid: 16498380
references.citation: J Virol. 1998 Feb;72(2):891-9
references.pmid: 9444980
references.citation: J Virol. 2000 Jun;74(11):5382-4
references.pmid: 10799619
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17264-9
references.pmid: 15563593
references.citation: J Virol. 2010 Nov;84(21):11152-63
references.pmid: 20719949
references.citation: Virology. 2002 Aug 15;300(1):92-9
references.pmid: 12202209
references.citation: Virology. 2006 Mar 1;346(1):219-28
references.pmid: 16325221
references.citation: MMWR Morb Mortal Wkly Rep. 2010 Feb 12;59(5):125-9
references.pmid: 20150887
references.citation: Commun Dis Public Health. 2002 Dec;5(4):311-3
references.pmid: 12564247
references.citation: Clin Infect Dis. 2008 Dec 1;47(11):1458-67
references.pmid: 18959494
references.citation: Euro Surveill. 2010 Apr 29;15(17):
references.pmid: 20460086
references.citation: J Virol. 2007 Oct;81(20):11116-27
references.pmid: 17686837
references.citation: J Med Virol. 2004 May;73(1):91-6
references.pmid: 15042654
references.citation: Vaccine. 2008 Jul 4;26(29-30):3601-7
references.pmid: 18539365
references.citation: Arch Virol. 1996;141(3-4):733-41
references.pmid: 8645109
references.citation: J Biol Chem. 2008 May 23;283(21):14269-76
references.pmid: 18362155
references.citation: Virology. 2011 Aug 15;417(1):126-36
references.pmid: 21676427
references.citation: J Virol. 2004 May;78(10):5068-78
references.pmid: 15113888
references.citation: Virology. 1990 Sep;178(1):247-53
references.pmid: 2389552
references.citation: Euro Surveill. 2010 Dec 16;15(50):
references.pmid: 21172171
references.citation: J Med Virol. 2003 Jun;70(2):287-92
references.pmid: 12696120
references.citation: Microbiol Immunol. 1996;40(4):271-5
references.pmid: 8709862
references.citation: Virology. 1997 Oct 27;237(2):249-60
references.pmid: 9356337
references.citation: J Virol. 2002 Dec;76(24):12683-90
references.pmid: 12438594
references.citation: Virol J. 2010 Oct 11;7:263
references.pmid: 20937132
references.citation: J Virol. 2002 Dec;76(24):12676-82
references.pmid: 12438593
references.citation: Vaccine. 2011 Apr 5;29(16):2850-5
references.pmid: 21334386
references.citation: J Virol. 2011 Jan;85(1):32-42
references.pmid: 20980504
references.citation: Virology. 2002 Nov 10;303(1):15-32
references.pmid: 12482655
references.citation: J Virol. 2003 Jun;77(11):6385-93
references.pmid: 12743296
references.citation: CMAJ. 2006 Aug 29;175(5):483-8
references.pmid: 16940266
references.citation: J Virol. 2011 Aug;85(16):8376-85
references.pmid: 21680523
references.citation: PLoS Pathog. 2009 Jul;5(7):e1000525
references.pmid: 19629176
references.citation: Virology. 2007 Nov 25;368(2):262-72
references.pmid: 17692882
references.citation: Virology. 2002 Nov 10;303(1):33-46
references.pmid: 12482656
references.citation: J Virol. 1990 Sep;64(9):4137-45
references.pmid: 2166809