Adenovirus prevents dsRNA formation by promoting efficient splicing of viral RNA.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
22 02 2022
22 02 2022
Historique:
accepted:
08
10
2021
revised:
10
09
2021
received:
13
07
2021
pubmed:
22
10
2021
medline:
16
4
2022
entrez:
21
10
2021
Statut:
ppublish
Résumé
Eukaryotic cells recognize intracellular pathogens through pattern recognition receptors, including sensors of aberrant nucleic acid structures. Sensors of double-stranded RNA (dsRNA) are known to detect replication intermediates of RNA viruses. It has long been suggested that annealing of mRNA from symmetrical transcription of both top and bottom strands of DNA virus genomes can produce dsRNA during infection. Supporting this hypothesis, nearly all DNA viruses encode inhibitors of dsRNA-recognition pathways. However, direct evidence that DNA viruses produce dsRNA is lacking. Contrary to dogma, we show that the nuclear-replicating DNA virus adenovirus (AdV) does not produce detectable levels of dsRNA during infection. In contrast, abundant dsRNA is detected within the nucleus of cells infected with AdV mutants defective for viral RNA processing. In the presence of nuclear dsRNA, the cytoplasmic dsRNA sensor PKR is relocalized and activated within the nucleus. Accumulation of viral dsRNA occurs in the late phase of infection, when unspliced viral transcripts form intron/exon base pairs between top and bottom strand transcripts. We propose that DNA viruses actively limit dsRNA formation by promoting efficient splicing and mRNA processing, thus avoiding detection and restriction by host innate immune sensors of pathogenic nucleic acids.
Identifiants
pubmed: 34671803
pii: 6406474
doi: 10.1093/nar/gkab896
pmc: PMC8860579
doi:
Substances chimiques
RNA, Double-Stranded
0
RNA, Messenger
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1201-1220Subventions
Organisme : NCI NIH HHS
ID : P01 CA196539
Pays : United States
Organisme : NIAID NIH HHS
ID : K99 AI159049
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145266
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118891
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121321
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI104887
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA115299
Pays : United States
Organisme : NIAID NIH HHS
ID : F32 AI138432
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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