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

Meng, Bo and Bentley, Kirsten and Marriott, Anthony C and Scott, Paul D and Dimmock, Nigel J and Easton, Andrew J (2017) Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA. Virology journal, 14 (1). p. 138. ISSN 1743-422X. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

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Official URL: https://virologyj.biomedcentral.com/articles/10.11...

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.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: WC Communicabable diseases
Divisions: Clinical Support > Pathology
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Depositing User: Mrs Semanti Chakraborty
Date Deposited: 27 Nov 2017 15:08
Last Modified: 27 Nov 2017 15:08
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1465

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