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Viruses 2016, 8(8), 237; doi:10.3390/v8080237

A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

1
Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
2
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 8 July 2016 / Revised: 12 August 2016 / Accepted: 15 August 2016 / Published: 22 August 2016
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [2291 KB, uploaded 22 August 2016]   |  

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. View Full-Text
Keywords: defective interfering; influenza virus; antiviral; human respiratory cells defective interfering; influenza virus; antiviral; human respiratory cells
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MDPI and ACS Style

Smith, C.M.; Scott, P.D.; O’Callaghan, C.; Easton, A.J.; Dimmock, N.J. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral. Viruses 2016, 8, 237.

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