Noncoding subgenomic flavivirus RNA: multiple functions in West Nile Virus pathogenesis and modulation of host responses

Roby, Justin A., Pijlman, Gorben P., Wilusz, Jeffrey and Khromykh, Alexander A. (2014) Noncoding subgenomic flavivirus RNA: multiple functions in West Nile Virus pathogenesis and modulation of host responses. Viruses, 6 2: 404-427. doi:10.3390/v6020404


Author Roby, Justin A.
Pijlman, Gorben P.
Wilusz, Jeffrey
Khromykh, Alexander A.
Title Noncoding subgenomic flavivirus RNA: multiple functions in West Nile Virus pathogenesis and modulation of host responses
Journal name Viruses   Check publisher's open access policy
ISSN 1999-4915
Publication date 2014-01-27
Year available 2014
Sub-type Article (original research)
DOI 10.3390/v6020404
Open Access Status DOI
Volume 6
Issue 2
Start page 404
End page 427
Total pages 24
Place of publication Basel, Switzerland
Publisher M D P I
Language eng
Abstract Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'-3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-/ by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.
Formatted abstract
Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.
Keyword Flavivirus
sfRNA
Replication
Pathogenicity
Interferon
RNAi
XRN1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special Issue: "West Nile Virus".

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 14 Feb 2014, 20:04:26 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences