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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| Vydáno v: | The Journal of infectious diseases Ročník 204 Suppl 3; s. S941 |
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| Hlavní autoři: | , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.11.2011
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| ISSN: | 1537-6613, 1537-6613 |
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| Abstract | 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. |
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| AbstractList | 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.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. 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. |
| Author | Volchkova, Valentina A Dolnik, Olga Volchkov, Viktor E Reynard, Olivier Martinez, Miguel J |
| Author_xml | – sequence: 1 givenname: Valentina A surname: Volchkova fullname: Volchkova, Valentina A organization: Filovirus Laboratory, INSERM U758, Human Virology Department, Université de Lyon, Claude Bernard Université Lyon-1, Ecole Normale Supérieure de Lyon, France – sequence: 2 givenname: Olga surname: Dolnik fullname: Dolnik, Olga – sequence: 3 givenname: Miguel J surname: Martinez fullname: Martinez, Miguel J – sequence: 4 givenname: Olivier surname: Reynard fullname: Reynard, Olivier – sequence: 5 givenname: Viktor E surname: Volchkov fullname: Volchkov, Viktor E |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21987773$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | 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 |
| Title | Genomic RNA editing and its impact on Ebola virus adaptation during serial passages in cell culture and infection of guinea pigs |
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