Ebolavirus polymerase uses an unconventional genome replication mechanism.
Ebola virus genome ends
Ebola virus replication
ebolavirus replication initiation
nonsegmented negative strand RNA virus replication
variable 3′ genome ends
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
pubmed:
10
4
2019
medline:
26
3
2020
entrez:
10
4
2019
Statut:
ppublish
Résumé
Most nonsegmented negative strand (NNS) RNA virus genomes have complementary 3' and 5' terminal nucleotides because the promoters at the 3' ends of the genomes and antigenomes are almost identical to each other. However, according to published sequences, both ends of ebolavirus genomes show a high degree of variability, and the 3' and 5' terminal nucleotides are not complementary. If correct, this would distinguish the ebolaviruses from other NNS RNA viruses. Therefore, we investigated the terminal genomic and antigenomic nucleotides of three different ebolavirus species, Ebola (EBOV), Sudan, and Reston viruses. Whereas the 5' ends of ebolavirus RNAs are highly conserved with the sequence ACAGG-5', the 3' termini are variable and are typically 3'-GCCUGU, ACCUGU, or CCUGU. A small fraction of analyzed RNAs had extended 3' ends. The majority of 3' terminal sequences are consistent with a mechanism of nucleotide addition by hairpin formation and back-priming. Using single-round replicating EBOV minigenomes, we investigated the effect of the 3' terminal nucleotide on viral replication and found that the EBOV polymerase initiates replication opposite the 3'-CCUGU motif regardless of the identity of the 3' terminal nucleotide(s) and of the position of this motif relative to the 3' end. Deletion or mutation of the first residue of the 3'-CCUGU motif completely abolished replication initiation, suggesting a crucial role of this nucleotide in directing initiation. Together, our data show that ebolaviruses have evolved a unique replication strategy among NNS RNA viruses resulting in 3' overhangs. This could be a mechanism to avoid antiviral recognition.
Identifiants
pubmed: 30962389
pii: 1815745116
doi: 10.1073/pnas.1815745116
pmc: PMC6486738
doi:
Substances chimiques
Nucleotides
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
8535-8543Subventions
Organisme : NIAID NIH HHS
ID : R01 AI113321
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI133486
Pays : United States
Organisme : NIAID NIH HHS
ID : R03 AI114293
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI126457
Pays : United States
Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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