Unexpected complexity in the interference activity of a cloned influenza defective interfering RNAReport as inadecuate

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Virology Journal

, 14:138

Influenza viruses


BackgroundDefective 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.

ResultsWe have investigated the RNA inhibitory mechanisms 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.

ConclusionsOur 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.

KeywordsInfluenza virus Defective interfering RNA Replication Interference AbbreviationscRNAPositive sense antigenome RNA

DIDefective interfering


GFPGreen fluorescent protein

ORFOpen reading frame

PCRPolymerase chain reaction


vRNANegative sense virion genomic RNA

VSVVesicular stomatitis virus

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Author: Bo Meng - Kirsten Bentley - Anthony C. Marriott - Paul D. Scott - Nigel J. Dimmock - Andrew J. Easton

Source: https://link.springer.com/

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