Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir

Nigel J. Dimmock*, Brian K. Dove, Bo Meng, Paul D. Scott, Irene Taylor, Linda Cheung, Bassam Hallis, Anthony C. Marriott, Miles Carroll, Andrew J. Easton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


The main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. These have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively rapidly. Defective interfering (DI) influenza virus is a natural antiviral that works in a different way to oseltamivir and zanamivir, and a cloned version (segment 1 244 DI RNA in a cloned A/PR/8/34 virus; 244/PR8) has proved effective in preclinical studies in mice. The active principle is the DI RNA, and this is thought to interact with all influenza A viruses by inhibiting RNA virus synthesis and packaging of the cognate virion RNA into nascent DI virus particles. We have compared the ability of DI virus and oseltamivir to protect ferrets from intranasal 2009 pandemic influenza virus A/California/04/09 (A/Cal, H1N1). Ferrets were treated with a single 2. μg intranasal dose of 244 DI RNA delivered as 244/PR8 virus, or a total of 25. mg/kg body weight of oseltamivir given as 10 oral doses over 5. days. Both DI virus and oseltamivir reduced day 2 infectivity and the influx of cells into nasal fluids, and permitted the development of adaptive immunity. However DI virus, but not oseltamivir, significantly reduced weight loss, facilitated better weight gain, reduced respiratory disease, and reduced infectivity on days 4 and 6. 244 DI RNA was amplified by A/Cal by >25,000-fold, consistent with the amelioration of clinical disease. Treatment with DI virus did not delay clearance or cause persistence of infectious virus or DI RNA. Thus in this system DI virus was overall more effective than oseltamivir in combatting pandemic A/California/04/09.

Original languageEnglish
Pages (from-to)376-385
Number of pages10
JournalAntiviral Research
Issue number3
Publication statusPublished - Dec 2012

Bibliographical note

Funding Information:
We acknowledge financial support from the Wellcome Trust Technology Transfer Award No. 090441Z09Z, and the National Institutes for Health Research, Porton for animal model development. We are grateful to Thomas Bean and the staff of the Biological Investigations Group at HPA for assistance in conducting the ferret studies and to Andrew Mead (University of Warwick) for assistance with the statistical analysis. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Health Protection Agency.


  • Defective interfering virus
  • Ferret
  • Influenza virus
  • Oseltamivir
  • Protection


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