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The influence of viral RNA secondary structure on interactions with innate host cell defences

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The influence of viral RNA secondary structure on interactions with innate host cell defences. / Witteveldt, Jeroen; Blundell, Richard; Maarleveld, Joris J.; McFadden, Nora; Evans, David J.; Simmonds, Peter.

In: Nucleic Acids Research, Vol. 42, No. 5, 03.2014, p. 3314-3329.

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Harvard

Witteveldt, J, Blundell, R, Maarleveld, JJ, McFadden, N, Evans, DJ & Simmonds, P 2014, 'The influence of viral RNA secondary structure on interactions with innate host cell defences' Nucleic Acids Research, vol. 42, no. 5, pp. 3314-3329. https://doi.org/10.1093/nar/gkt1291

APA

Witteveldt, J., Blundell, R., Maarleveld, J. J., McFadden, N., Evans, D. J., & Simmonds, P. (2014). The influence of viral RNA secondary structure on interactions with innate host cell defences. Nucleic Acids Research, 42(5), 3314-3329. https://doi.org/10.1093/nar/gkt1291

Vancouver

Witteveldt J, Blundell R, Maarleveld JJ, McFadden N, Evans DJ, Simmonds P. The influence of viral RNA secondary structure on interactions with innate host cell defences. Nucleic Acids Research. 2014 Mar;42(5):3314-3329. https://doi.org/10.1093/nar/gkt1291

Author

Witteveldt, Jeroen ; Blundell, Richard ; Maarleveld, Joris J. ; McFadden, Nora ; Evans, David J. ; Simmonds, Peter. / The influence of viral RNA secondary structure on interactions with innate host cell defences. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 5. pp. 3314-3329.

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@article{02eba02702af4f95a357b1f63fdd2086,
title = "The influence of viral RNA secondary structure on interactions with innate host cell defences",
abstract = "RNA viruses infecting vertebrates differ fundamentally in their ability to establish persistent infections with markedly different patterns of transmission, disease mechanisms and evolutionary relationships with their hosts. Although interactions with host innate and adaptive responses are complex and persistence mechanisms likely multi-factorial, we previously observed associations between bioinformatically predicted RNA secondary formation in genomes of positive-stranded RNA viruses with their in vivo fitness and persistence. To analyse this interactions functionally, we transfected fibroblasts with non-replicating, non-translated RNA transcripts from RNA viral genomes with differing degrees of genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts induced interferon-beta mediated though RIG-I and PKR activation, the latter associated with rapid induction of antiviral stress granules. A striking inverse correlation was observed between induction of both cellular responses with transcript RNA structure formation that was independent of both nucleotide composition and sequence length. The consistent inability of cells to recognize RNA transcripts possessing GORS extended to downstream differences from unstructured transcripts in expression of TNF-alpha, other interferon-stimulated genes and induction of apoptosis. This functional association provides novel insights into interactions between virus and host early after infection and provides evidence for a novel mechanism for evading intrinsic and innate immune responses.",
keywords = "Double-stranded-RNA, Hepatitis-C virus, Protein-kinase PKR, Acting replication element, Target site accessibility",
author = "Jeroen Witteveldt and Richard Blundell and Maarleveld, {Joris J.} and Nora McFadden and Evans, {David J.} and Peter Simmonds",
note = "Funding for open access charge: Wellcome Trust [WT087628MA]. Date of Acceptance: 19/11/2013",
year = "2014",
month = "3",
doi = "10.1093/nar/gkt1291",
language = "English",
volume = "42",
pages = "3314--3329",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "OXFORD UNIV PRESS",
number = "5",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The influence of viral RNA secondary structure on interactions with innate host cell defences

AU - Witteveldt, Jeroen

AU - Blundell, Richard

AU - Maarleveld, Joris J.

AU - McFadden, Nora

AU - Evans, David J.

AU - Simmonds, Peter

N1 - Funding for open access charge: Wellcome Trust [WT087628MA]. Date of Acceptance: 19/11/2013

PY - 2014/3

Y1 - 2014/3

N2 - RNA viruses infecting vertebrates differ fundamentally in their ability to establish persistent infections with markedly different patterns of transmission, disease mechanisms and evolutionary relationships with their hosts. Although interactions with host innate and adaptive responses are complex and persistence mechanisms likely multi-factorial, we previously observed associations between bioinformatically predicted RNA secondary formation in genomes of positive-stranded RNA viruses with their in vivo fitness and persistence. To analyse this interactions functionally, we transfected fibroblasts with non-replicating, non-translated RNA transcripts from RNA viral genomes with differing degrees of genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts induced interferon-beta mediated though RIG-I and PKR activation, the latter associated with rapid induction of antiviral stress granules. A striking inverse correlation was observed between induction of both cellular responses with transcript RNA structure formation that was independent of both nucleotide composition and sequence length. The consistent inability of cells to recognize RNA transcripts possessing GORS extended to downstream differences from unstructured transcripts in expression of TNF-alpha, other interferon-stimulated genes and induction of apoptosis. This functional association provides novel insights into interactions between virus and host early after infection and provides evidence for a novel mechanism for evading intrinsic and innate immune responses.

AB - RNA viruses infecting vertebrates differ fundamentally in their ability to establish persistent infections with markedly different patterns of transmission, disease mechanisms and evolutionary relationships with their hosts. Although interactions with host innate and adaptive responses are complex and persistence mechanisms likely multi-factorial, we previously observed associations between bioinformatically predicted RNA secondary formation in genomes of positive-stranded RNA viruses with their in vivo fitness and persistence. To analyse this interactions functionally, we transfected fibroblasts with non-replicating, non-translated RNA transcripts from RNA viral genomes with differing degrees of genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts induced interferon-beta mediated though RIG-I and PKR activation, the latter associated with rapid induction of antiviral stress granules. A striking inverse correlation was observed between induction of both cellular responses with transcript RNA structure formation that was independent of both nucleotide composition and sequence length. The consistent inability of cells to recognize RNA transcripts possessing GORS extended to downstream differences from unstructured transcripts in expression of TNF-alpha, other interferon-stimulated genes and induction of apoptosis. This functional association provides novel insights into interactions between virus and host early after infection and provides evidence for a novel mechanism for evading intrinsic and innate immune responses.

KW - Double-stranded-RNA

KW - Hepatitis-C virus

KW - Protein-kinase PKR

KW - Acting replication element

KW - Target site accessibility

U2 - 10.1093/nar/gkt1291

DO - 10.1093/nar/gkt1291

M3 - Article

VL - 42

SP - 3314

EP - 3329

JO - Nucleic Acids Research

T2 - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 5

ER -

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ID: 211241627