We have shown that non-cloned and cloned DI influenza A viruses protect mice from lethal infection caused by influenza A virus (Dimmock et al., 1986, Dimmock et al., 2008, Morgan et al., 1993 and Noble and Dimmock, 1994). Only a single dose of cloned 244/PR8 virus is needed and the DI RNA is amplified by the infecting virus (Scott et al., 2011a). Protection lasts for one to several weeks depending on the initial dose of GSK-3 assay DI virus (Dimmock et al., 2008 and Scott et al., 2011a). Post-infection treatment is effective for

up to 2 days after infection (Dimmock et al., 2008). Influenza viruses usually have to be adapted to grow in mice whereas the ferret is highly susceptible to new human isolates (Francis,

1934, Shope, 1931 and Smith et al., 1933). Because humans and ferrets develop a very similar disease the ferret is the preferred model for human influenza (Barnard, 2009, Cameron et al., 2008, Herlocher et al., 2001, Matsuoka et al., 2009 and Smith and Sweet, 1988; van den Brand et al., 2010; Whitley, 2010). In a preliminary study in ferrets we tested a non-cloned DI influenza virus preparation that contained an unspecified Palbociclib nmr collection of DI RNAs derived from an equine influenza A virus, and showed that it afforded ferrets some protection against an H3N2 challenge virus (Mann et al., 2006). More recently we used a cloned 244/PR8 virus (Dimmock et al., 2008) reconstructed with a PR8 hemagglutinin variant that bound to both α 2,6- and α 2,3-linked sialyl receptors (Meng et al., 2010), so that DI RNA would be delivered to and protect cells bearing

both types of receptor. There are a number of studies of pandemic these H1N1 in ferrets (Itoh et al., 2009, Maines et al., 2009, Munster et al., 2009 and van den Brand et al., 2010). Pandemic 2009 H1N1 viruses differ from seasonal H1N1 viruses in a number of ways: the former use 2,6- and 2,3-linked receptors (Childs et al., 2009), preferentially infect the lower respiratory tract in humans and in animal models (Guarner and Falcon-Escobedo, 2009), replicate in the lower respiratory tract of ferrets rather than the nasal cavity (Munster et al., 2009 and van den Brand et al., 2010), and cause more severe pathological lesions than seasonal H1N1 virus in mice, ferrets and non-human primates (Itoh et al., 2009). In addition to vaccines (Cox and Bridges, 2007, Nichol, 2008 and Treanor, 2004) antivirals directed against the virus neuraminidase have become an important addition to the armoury providing relief from influenza disease (Colman, 2009, Oxford, 2007 and Smith et al., 2006). The antivirals oseltamivir and zanamivir protect against all influenza A and B strains (Jefferson et al., 2009). Oseltamivir, taken orally, and zanamivir, a nasal spray, are administered twice daily, and are most effective when taken before or soon after infection.