Abstract:
UNLABELLED:Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis. Vaccination against mumps virus has been effective in reducing mumps cases. However, recently large outbreaks have occurred in vaccinated populations. There is no anti-MuV drug. Understanding replication of MuV may lead to novel antiviral strategies. MuV RNA-dependent RNA polymerase minimally consists of the phosphoprotein (P) and the large protein (L). The P protein is heavily phosphorylated. To investigate the roles of serine (S) and threonine (T) residues of P in viral RNA transcription and replication, P was subjected to mass spectrometry and mutational analysis. P, a 392-amino acid residue protein, has 64 S and T residues. We have found that mutating nine S/T residues significantly reduced and mutating residue T at 101 to A (T101A) significantly enhanced activity in a minigenome system. A recombinant virus containing the P-T101A mutation (rMuV-P-T101A) was recovered and analyzed. rMuV-P-T101A grew to higher titers and had increased protein expression at early time points. Together, these results suggest that phosphorylation of MuV-P-T101 plays a negative role in viral RNA synthesis. This is the first time that the P protein of a paramyxovirus has been systematically analyzed for S/T residues that are critical for viral RNA synthesis. IMPORTANCE:Mumps virus (MuV) is a reemerging paramyxovirus that caused large outbreaks in the United States, where vaccination coverage is very high. There is no anti-MuV drug. In this work, we have systematically analyzed roles of Ser/Thr residues of MuV P in viral RNA synthesis. We have identified S/T residues of P critical for MuV RNA synthesis and phosphorylation sites that are important for viral RNA synthesis. This work leads to a better understanding of viral RNA synthesis as well as to potential novel strategies to control mumps.
journal_name
J Viroljournal_title
Journal of virologyauthors
Pickar A,Xu P,Elson A,Li Z,Zengel J,He Bdoi
10.1128/JVI.03673-13subject
Has Abstractpub_date
2014-04-01 00:00:00pages
4414-22issue
8eissn
0022-538Xissn
1098-5514pii
JVI.03673-13journal_volume
88pub_type
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更新日期:2014-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.67.5.2922-2927.1993
更新日期:1993-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.3154-3162.1994
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doi:10.1128/JVI.00232-08
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pub_type: 杂志文章
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journal_title:Journal of virology
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doi:10.1128/JVI.72.1.731-738.1998
更新日期:1998-01-01 00:00:00
abstract::PLC/PRF/5, a tissue culture cell line isolated from a human hepatocellular carcinoma and producing hepatitis B surface antigen, was studied for the presence of hepatitis B virus (HBV)-specific DNA and RNA. PLC/PRF/5 cell DNA accelerated the rate of reassociation of HBV [32P]DNA, and quantitative experiments indicated ...
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更新日期:1980-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.2.1030-1036.1995
更新日期:1995-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1981-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05039-11
更新日期:2011-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01357-19
更新日期:2020-01-31 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4470-4478.1992
更新日期:1992-07-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, but no safe and effective RSV vaccine is yet available. For reasons that are not well understood, RSV is only weakly immunogenic, and reinfection occurs throughout life. This has complicated the sea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.3.1130-1139.2006
更新日期:2006-02-01 00:00:00