The R2TP complex regulates paramyxovirus RNA synthesis
| Autor: | Tsuyoshi Sekizuka, Minoru Kidokoro, Reiko Nakagawa, Yuichiro Nakatsu, Fumihiro Kato, Masafumi Sakata, Hiroshi Katoh, Makoto Kuroda, Naganori Nao, Makoto Takeda |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Small interfering RNA
Physiology viruses Virus Replication Biochemistry Immune Physiology Gene expression Medicine and Health Sciences Small interfering RNAs Biology (General) Immune Response Host factor 0303 health sciences Viral Genomics Immune System Proteins 030302 biochemistry & molecular biology Genomics Cell biology Precipitation Techniques Nucleic acids Mumps virus Host-Pathogen Interactions 293T cells Cell lines RNA Viral Biological cultures Research Article QH301-705.5 Nucleic acid synthesis Immunology Microbial Genomics Biology Microbiology Antibodies 03 medical and health sciences Viral Proteins Virology Genetics Gene silencing Immunoprecipitation Humans Chemical synthesis HSP90 Heat-Shock Proteins RNA synthesis Non-coding RNA Molecular Biology Mumps 030304 developmental biology R2TP complex Innate immune system Biology and life sciences RNA Proteins RC581-607 biochemical phenomena metabolism and nutrition Gene regulation Research and analysis methods Biosynthetic techniques Viral replication A549 Cells Parasitology Immunologic diseases. Allergy |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 15, Iss 5, p e1007749 (2019) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | The regulation of paramyxovirus RNA synthesis by host proteins is poorly understood. Here, we identified a novel regulation mechanism of paramyxovirus RNA synthesis by the Hsp90 co-chaperone R2TP complex. We showed that the R2TP complex interacted with the paramyxovirus polymerase L protein and that silencing of the R2TP complex led to uncontrolled upregulation of mumps virus (MuV) gene transcription but not genome replication. Regulation by the R2TP complex was critical for MuV replication and evasion of host innate immune responses. The R2TP complex also regulated measles virus (MeV) RNA synthesis, but its function was inhibitory and not beneficial to MeV, as MeV evaded host innate immune responses in the absence of the R2TP complex. The identification of the R2TP complex as a critical host factor sheds new light on the regulation of paramyxovirus RNA synthesis. Author summary The family Paramyxoviridae includes several important human and animal pathogens such as mumps virus (MuV) and measles virus (MeV). Paramyxovirus RNA synthesis is strictly regulated by both viral and host proteins. In this study, we identified the R2TP complex as a novel host factor regulating paramyxovirus RNA synthesis. The R2TP complex is a Hsp90 co-chaperone and is involved in Hsp90-mediated assembly of large protein complexes. We showed that the R2TP complex precisely regulated MuV transcription by interacting with the polymerase L protein. This regulation was critical for MuV evasion of host innate immune responses and for viral replication. We also showed that the R2TP complex regulated MeV RNA synthesis, but that its function was inhibitory and not beneficial to MeV. Our findings support a novel regulation mechanism of paramyxovirus RNA synthesis that is directly relevant to its biology and life cycle, and provide the first evidence linking the R2TP complex to defense against viral infection. |
| Databáze: | OpenAIRE |
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