Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
J Virol. 2014 Apr;88(8):4414-22. doi: 10.1128/JVI.03673-13. Epub 2014 Feb 5.
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.
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.
腮腺炎病毒（MuV）是一种重新出现的副粘病毒，在美国造成了大规模爆发，而美国的疫苗接种覆盖率非常高。目前还没有抗 MuV 的药物。在这项工作中，我们系统地分析了 MuV P 蛋白中 Ser/Thr 残基在病毒 RNA 合成中的作用。我们确定了 P 蛋白中对 MuV RNA 合成至关重要的 S/T 残基和对病毒 RNA 合成很重要的磷酸化位点。这项工作使我们更好地理解了病毒 RNA 合成，并为控制腮腺炎提供了潜在的新策略。
