, 2008). Fig. 5a summarizes the mean values per ferret group per day, and Fig. 5b show values for individual animals. The data show that 244 DI virus RNA was marginally above detectable levels at 1 day after infection, and that by day 2 there were high levels of 244 DI virus RNA in infected ferrets treated with 244

DI virus. 244 DI virus RNA was not detected in the other groups indicating Protease Inhibitor Library that 244 DI virus RNA is specific for ferrets inoculated with 244 DI virus. The 244 DI virus RNA levels increased by nearly 1000-fold between days 1 and 2, and by over 25,000-fold between days 1 and 3, reaching a peak of 1010.8 copies per ferret. 244 DI virus RNA then steadily declined reaching a very low level on day 10 and was undetectable on day 14 after infection. These data demonstrate the ability of the find more 244 DI virus RNA to be amplified by the very agent that it is acting against – in this case A/Cal influenza virus. The >25,000-fold expansion factor effectively augments the applied dose of 244 DI virus RNA from 2 μg to >50 mg per animal. In addition to the signs and symptoms described above ferrets were monitored

in the morning and the afternoon for loss of appetite, appearance of diarrhoea, and reduction in activity. None of these was seen in any group. There was a strong HI antibody response to A/Cal/04/09 (H1N1) in sera taken at 14 days after infection whether groups had been treated with 244 DI virus, oseltamivir or were untreated (Table 2). The titre of 244 DI-treated infected group was significantly higher than the infected group treated

with oseltamivir (p = 0.008). Oxymatrine Thus amelioration of infection by 244 DI virus appeared to improve rather than diminish the antibody response to the A/Cal haemagglutinin. In this study we compared the effects of treatment with DI virus and oseltamivir on the course of disease and virus load resulting from infection with 2009 pandemic influenza A virus (A/California/04/09) in the ferret. Data summarized in Table 3 show that DI virus reduced fever, weight loss, respiratory symptoms (sneezing and nasal discharge), the appearance of cells in nasal washes, and virus load. All this was coincident with a dramatic increase in DI RNA, presumably due to its amplification by A/Cal. It is reasonable to suppose that the beneficial effects are the result of the action of this augmented population of DI RNA. Augmentation of 244 DI RNA is consistent with the mouse model in which amplification of 244 DI virus RNA by various influenza A viruses has been documented many times (Dimmock et al., 2008 and Scott et al., 2011a). It is likely that 244 RNA in nasal washes is packaged into newly synthesised DI virus particles as influenza RNA either free or in a ribonucleoprotein structure is susceptible to degradation by ribonuclease (Duesberg, 1969).