The C-Terminal Domain of the Sudan Ebolavirus L Protein Is Essential for RNA Binding and Methylation.
J Virol
; 94(12)2020 06 01.
Article
em En
| MEDLINE
| ID: mdl-32269120
ABSTRACT
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 cap-independent 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.
Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA Polimerase Dependente de RNA
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RNA Viral
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Proteínas não Estruturais Virais
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Ebolavirus
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Metiltransferases
Limite:
Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França