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The C-Terminal Domain of the Sudan Ebolavirus L Protein Is Essential for RNA Binding and Methylation
- Source :
- Journal of Virology, Journal of Virology, 2020, 94 (12), pp.e00520-20. ⟨10.1128/JVI.00520-20⟩, Journal of Virology, American Society for Microbiology, 2020, 94 (12), pp.e00520-20. ⟨10.1128/JVI.00520-20⟩, J Virol
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- International audience; The large (L) protein of Ebola virus is a key protein for virus replication. Its N-terminal region harbors the RNA-dependent RNA polymerase activity, and its C terminus contains a cap assembling line composed of a capping domain and a methyltransferase domain (MTase) followed by a C-terminal domain (CTD) of unknown function. The L protein MTase catalyzes methylation at the 2'-O and N-7 positions of the cap structures. In addition, the MTase of Ebola virus can induce capin-dependent internal adenosine 2'-O-methylation. In this work, we investigated the CTD role in the regulation of the cap-dependent and cap-independent MTase activities of the L protein. We found that the CTD, which is enriched in basic amino acids, plays a key role in RNA binding and in turn regulates the different MTase activities. We demonstrated that the mutation of CTD residues modulates specifically the different MTase activities. Altogether, our results highlight the pivotal role of the L protein CTD in the control of viral RNA methylation, which is critical for Ebola virus replication and escape from the innate response in infected cells.IMPORTANCE Ebola virus infects human and nonhuman primates, causing severe infections that are often fatal. The epidemics, in West and Central Africa, emphasize the urgent need to develop antiviral therapies. The Ebola virus large protein (L), which is the central protein for viral RNA replication/transcription, harbors a methyltransferase domain followed by a C-terminal domain of unknown function. We show that the C-terminal domain regulates the L protein methyltransferase activities and consequently participates in viral replication and escape of the host innate immunity.
- Subjects :
- Models, Molecular
Protein Conformation, alpha-Helical
NS5
viruses
Gene Expression
Viral Nonstructural Proteins
Virus Replication
medicine.disease_cause
chemistry.chemical_compound
0302 clinical medicine
CAPPING ENZYME
Transcription (biology)
RNA polymerase
TRANSCRIPTION
Cloning, Molecular
0303 health sciences
POLYMERASE
Methylation
VESICULAR STOMATITIS-VIRUS
Ebolavirus
CAP
Recombinant Proteins
Genome Replication and Regulation of Viral Gene Expression
3. Good health
Host-Pathogen Interactions
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
RNA, Viral
Domain of unknown function
MESSENGER-RNA
METHYLTRANSFERASE DOMAIN
Protein Binding
Signal Transduction
Immunology
Biology
Microbiology
03 medical and health sciences
Protein Domains
Virology
Escherichia coli
medicine
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
030304 developmental biology
Ebola virus
Base Sequence
Sequence Homology, Amino Acid
IDENTIFICATION
C-terminus
RNA
Methyltransferases
RNA-Dependent RNA Polymerase
Gene Expression Regulation
chemistry
Viral replication
Insect Science
REPLICATION
Protein Conformation, beta-Strand
Sequence Alignment
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X and 10985514
- Database :
- OpenAIRE
- Journal :
- Journal of Virology, Journal of Virology, 2020, 94 (12), pp.e00520-20. ⟨10.1128/JVI.00520-20⟩, Journal of Virology, American Society for Microbiology, 2020, 94 (12), pp.e00520-20. ⟨10.1128/JVI.00520-20⟩, J Virol
- Accession number :
- edsair.doi.dedup.....4c4f8be8a801b8a5546aff3ff11246ad