Regulation of Mumps Virus Replication and Transcription by Kinase RPS6KB1.
J Virol
; 94(12)2020 06 01.
Article
en En
| MEDLINE
| ID: mdl-32295907
ABSTRACT
Mumps virus (MuV) caused the most viral meningitis before mass immunization. Unfortunately, MuV has reemerged in the United States in the past several years. MuV is a member of the genus Rubulavirus, in the family Paramyxoviridae, and has a nonsegmented negative-strand RNA genome. The viral RNA-dependent RNA polymerase (vRdRp) of MuV consists of the large protein (L) and the phosphoprotein (P), while the nucleocapsid protein (NP) encapsulates the viral RNA genome. These proteins make up the replication and transcription machinery of MuV. The P protein is phosphorylated by host kinases, and its phosphorylation is important for its function. In this study, we performed a large-scale small interfering RNA (siRNA) screen targeting host kinases that regulated MuV replication. The human kinase ribosomal protein S6 kinase beta-1 (RPS6KB1) was shown to play a role in MuV replication and transcription. We have validated the role of RPS6KB1 in regulating MuV using siRNA knockdown, an inhibitor, and RPS6KB1 knockout cells. We found that MuV grows better in cells lacking RPS6KB1, indicating that it downregulates viral growth. Furthermore, we detected an interaction between the MuV P protein and RPS6KB1, suggesting that RPS6KB1 directly regulates MuV replication and transcription.IMPORTANCE Mumps virus is an important human pathogen. In recent years, MuV has reemerged in the United State, with outbreaks occurring in young adults who have been vaccinated. Our work provides insight into a previously unknown mumps virus-host interaction. RPS6KB1 negatively regulates MuV replication, likely through its interaction with the P protein. Understanding virus-host interactions can lead to novel antiviral drugs and enhanced vaccine production.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
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Proteínas Virales
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ARN Polimerasa Dependiente del ARN
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Genoma Viral
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Proteínas de la Nucleocápside
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Proteínas Quinasas S6 Ribosómicas 70-kDa
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Virus de la Parotiditis
Límite:
Animals
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Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article