Genomic RNA editing and its impact on Ebola virus adaptation during serial passages in cell culture and infection of guinea pigs

Synthesis of the structural, surface glycoprotein (GP) of Ebola virus (EBOV) is dependent on transcriptional RNA editing phenomenon. Editing results in the insertion of an extra adenosine by viral polymerase at the editing site (7 consecutive template uridines) during transcription of GP gene of the...

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Vydané v:The Journal of infectious diseases Ročník 204 Suppl 3; s. S941
Hlavní autori: Volchkova, Valentina A, Dolnik, Olga, Martinez, Miguel J, Reynard, Olivier, Volchkov, Viktor E
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.11.2011
Predmet:
Adaptation, Physiological
Animals
Cercopithecus aethiops
Ebolavirus - genetics
Ebolavirus - physiology
Female
Gene Expression Regulation, Viral - physiology
Genome, Viral - genetics
Guinea Pigs
Hemorrhagic Fever, Ebola - virology
RNA Editing - physiology
RNA, Viral - genetics
Serial Passage
Vero Cells
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Replication - physiology
ISSN:1537-6613, 1537-6613
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Shrnutí:Synthesis of the structural, surface glycoprotein (GP) of Ebola virus (EBOV) is dependent on transcriptional RNA editing phenomenon. Editing results in the insertion of an extra adenosine by viral polymerase at the editing site (7 consecutive template uridines) during transcription of GP gene of the wild-type virus (EBOV/7U). In this study, we demonstrate that passage of EBOV/7U in Vero E6 cells results in the appearance and rapid accumulation of a variant (EBOV/8U) containing an additional uridine at the editing site in the viral genome. EBOV/8U outgrows and eventually replaces the wild-type EBOV during 4-5 passages. On the contrary, infection of guinea pigs with EBOV/8U leads to the appearance and rapid predominance by EBOV/7U. These rapid conversions suggest that editing of the genomic RNA occurs at a higher frequency than previously thought. In addition, it indicates that the EBOV/7U phenotype has a selective advantage that is linked to controlled expression of GP and/or expression of secreted sGP, the primary gene product for wild-type EBOV. This study demonstrates the potential for insertion and deletion of uridines in the editing site of the EBOV genomic RNA, depending on environmental constraints.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1537-6613
1537-6613
DOI:10.1093/infdis/jir321