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Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA

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Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA. / Meng, Bo; Bentley, Kirsten; Marriott, Anthony C.; Scott, Paul D.; Dimmock, Nigel J.; Easton, Andrew J.

In: Virology Journal, Vol. 14, No. 1, 138, 24.07.2017.

Research output: Contribution to journalArticle

Harvard

Meng, B, Bentley, K, Marriott, AC, Scott, PD, Dimmock, NJ & Easton, AJ 2017, 'Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA' Virology Journal, vol. 14, no. 1, 138. https://doi.org/10.1186/s12985-017-0805-6

APA

Meng, B., Bentley, K., Marriott, A. C., Scott, P. D., Dimmock, N. J., & Easton, A. J. (2017). Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA. Virology Journal, 14(1), [138]. https://doi.org/10.1186/s12985-017-0805-6

Vancouver

Meng B, Bentley K, Marriott AC, Scott PD, Dimmock NJ, Easton AJ. Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA. Virology Journal. 2017 Jul 24;14(1). 138. https://doi.org/10.1186/s12985-017-0805-6

Author

Meng, Bo ; Bentley, Kirsten ; Marriott, Anthony C. ; Scott, Paul D. ; Dimmock, Nigel J. ; Easton, Andrew J. / Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA. In: Virology Journal. 2017 ; Vol. 14, No. 1.

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@article{69bb1adc5ed74bc595ceca40e5429b03,
title = "Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA",
abstract = "Background:  Defective interfering (DI) viruses are natural antivirals made by nearly all viruses. They have a highly deleted genome (thus being non-infectious) and interfere with the replication of genetically related infectious viruses. We have produced the first potential therapeutic DI virus for the clinic by cloning an influenza A DI RNA (1/244) which was derived naturally from genome segment 1. This is highly effective in vivo, and has unexpectedly broad-spectrum activity with two different modes of action: inhibiting influenza A viruses through RNA interference, and all other (interferon-sensitive) respiratory viruses through stimulating interferon type I.Results:  We have investigated the RNA inhibitory mechanism(s) of DI 1/244 RNA. Ablation of initiation codons does not diminish interference showing that no protein product is required for protection. Further analysis indicated that 1/244 DI RNA interferes by replacing the cognate full-length segment 1 RNA in progeny virions, while interfering with the expression of genome segment 1, its cognate RNA, and genome RNAs 2 and 3, but not genome RNA 6, a representative of the non-polymerase genes.Conclusions:  Our data contradict the dogma that a DI RNA only interferes with expression from its cognate full-length segment. There is reciprocity as cloned segment 2 and 3 DI RNAs inhibited expression of RNAs from a segment 1 target. These data demonstrate an unexpected complexity in the mechanism of interference by this cloned therapeutic DI RNA.",
keywords = "Influenza virus, Defective interfering RNA, Replication, Interference",
author = "Bo Meng and Kirsten Bentley and Marriott, {Anthony C.} and Scott, {Paul D.} and Dimmock, {Nigel J.} and Easton, {Andrew J.}",
note = "Funding: Medical Research Council (Grant No. G0600832).",
year = "2017",
month = "7",
day = "24",
doi = "10.1186/s12985-017-0805-6",
language = "English",
volume = "14",
journal = "Virology Journal",
issn = "1743-422X",
publisher = "BioMed Central",
number = "1",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA

AU - Meng, Bo

AU - Bentley, Kirsten

AU - Marriott, Anthony C.

AU - Scott, Paul D.

AU - Dimmock, Nigel J.

AU - Easton, Andrew J.

N1 - Funding: Medical Research Council (Grant No. G0600832).

PY - 2017/7/24

Y1 - 2017/7/24

N2 - Background:  Defective interfering (DI) viruses are natural antivirals made by nearly all viruses. They have a highly deleted genome (thus being non-infectious) and interfere with the replication of genetically related infectious viruses. We have produced the first potential therapeutic DI virus for the clinic by cloning an influenza A DI RNA (1/244) which was derived naturally from genome segment 1. This is highly effective in vivo, and has unexpectedly broad-spectrum activity with two different modes of action: inhibiting influenza A viruses through RNA interference, and all other (interferon-sensitive) respiratory viruses through stimulating interferon type I.Results:  We have investigated the RNA inhibitory mechanism(s) of DI 1/244 RNA. Ablation of initiation codons does not diminish interference showing that no protein product is required for protection. Further analysis indicated that 1/244 DI RNA interferes by replacing the cognate full-length segment 1 RNA in progeny virions, while interfering with the expression of genome segment 1, its cognate RNA, and genome RNAs 2 and 3, but not genome RNA 6, a representative of the non-polymerase genes.Conclusions:  Our data contradict the dogma that a DI RNA only interferes with expression from its cognate full-length segment. There is reciprocity as cloned segment 2 and 3 DI RNAs inhibited expression of RNAs from a segment 1 target. These data demonstrate an unexpected complexity in the mechanism of interference by this cloned therapeutic DI RNA.

AB - Background:  Defective interfering (DI) viruses are natural antivirals made by nearly all viruses. They have a highly deleted genome (thus being non-infectious) and interfere with the replication of genetically related infectious viruses. We have produced the first potential therapeutic DI virus for the clinic by cloning an influenza A DI RNA (1/244) which was derived naturally from genome segment 1. This is highly effective in vivo, and has unexpectedly broad-spectrum activity with two different modes of action: inhibiting influenza A viruses through RNA interference, and all other (interferon-sensitive) respiratory viruses through stimulating interferon type I.Results:  We have investigated the RNA inhibitory mechanism(s) of DI 1/244 RNA. Ablation of initiation codons does not diminish interference showing that no protein product is required for protection. Further analysis indicated that 1/244 DI RNA interferes by replacing the cognate full-length segment 1 RNA in progeny virions, while interfering with the expression of genome segment 1, its cognate RNA, and genome RNAs 2 and 3, but not genome RNA 6, a representative of the non-polymerase genes.Conclusions:  Our data contradict the dogma that a DI RNA only interferes with expression from its cognate full-length segment. There is reciprocity as cloned segment 2 and 3 DI RNAs inhibited expression of RNAs from a segment 1 target. These data demonstrate an unexpected complexity in the mechanism of interference by this cloned therapeutic DI RNA.

KW - Influenza virus

KW - Defective interfering RNA

KW - Replication

KW - Interference

U2 - 10.1186/s12985-017-0805-6

DO - 10.1186/s12985-017-0805-6

M3 - Article

VL - 14

JO - Virology Journal

T2 - Virology Journal

JF - Virology Journal

SN - 1743-422X

IS - 1

M1 - 138

ER -

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ID: 250562590