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A defective interfering influenza RNA inhibits infectious influenza virus replication in human respiratory tract cells : a potential new human antiviral

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Smith, Claire, Scott, Paul, O’Callaghan, Christopher, Easton, A. J. (Andrew J.) and Dimmock, N. J. (2016) A defective interfering influenza RNA inhibits infectious influenza virus replication in human respiratory tract cells : a potential new human antiviral. Viruses, 8 (8). 237. doi:10.3390/v8080237 ISSN 1999-4915.

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Official URL: http://dx.doi.org/10.3390/v8080237

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Abstract

Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Influenza A virus -- Genetics, Antiviral agents, Respiratory infections, Bronchi -- Diseases, Lungs -- Diseases, Viruses -- Reproduction, RNA, Genomes, Fibroblasts, Epithelial cells
Journal or Publication Title: Viruses
Publisher: MDPI AG
ISSN: 1999-4915
Official Date: 22 August 2016
Dates:
DateEvent
22 August 2016Published
15 August 2016Accepted
8 July 2016Submitted
Volume: 8
Number: 8
Article Number: 237
DOI: 10.3390/v8080237
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 24 August 2016
Date of first compliant Open Access: 1 June 2018
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
09044 1Z09ZWellcome Trusthttp://dx.doi.org/10.13039/100004440

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