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

• Published in: Viruses Vol. 8; no. 8; p. 237
• Main Authors: Smith, Claire, Scott, Paul, O’Callaghan, Christopher, Easton, Andrew, Dimmock, Nigel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 22.08.2016; MDPI AG
• Subjects: Administration, Intranasal; Animals; antiviral; Antiviral Agents - administration & dosage; Antiviral Agents - metabolism; defective interfering; Defective Viruses - genetics; Disease Models, Animal; Epithelial Cells - virology; Ferrets; Fibroblasts - virology; human respiratory cells; Humans; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - physiology; influenza virus; Mice; Orthomyxoviridae Infections - prevention & control; RNA, Viral - administration & dosage; RNA, Viral - metabolism; Virus Replication - drug effects; defective interfering; influenza virus; human respiratory cells; antiviral
• DOI: 10.3390/v8080237
• ISSN: 1999-4915

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.