6-fold) than those treated with oseltamivir. There was no difference in the time of respiratory disease between the 244 DI virus-treated group and the oseltamivir-treated group. The appearance of a cell infiltrate in nasal washes is a general response to respiratory infection in ferrets. On day 2 the influx of cells in control Natural Product Library A/Cal-infected animals was significantly reduced 5-fold by treatment with 244 DI virus and 9.6-fold by oseltamivir (Table 1). On day 3 cell influx was again significantly reduced 1.8-fold by 244 DI virus and 10.7-fold by oseltamivir. However, despite the

apparently higher reduction by oseltamivir, the outcome of the two treatments did not differ significantly (Table 1). By day 4 cell infiltration had increased in all groups to a similar level, approximately 100-fold above background. This remained at a plateau for around 8–10 days and then slowly decreased. Cell levels were still elevated by approximately 10-fold on day 14 when the study SCH727965 purchase was terminated, although the level in the 244 DI virus-treated infected ferrets was 2.5-fold lower than in oseltamivir-treated infected animals (Table 1). Infectious virus in the control A/Cal-infected group was just above background on day 1 after infection, and by day

2 had increased by more than 100-fold to 105.6 ffu per ferret (Fig. 4a). The levels of infectious virus detected on day 2 in the 244 DI virus-treated, infected group was 62-fold lower, and the oseltamivir-treated group was 200-fold lower (Fig. 4b). The difference between infectivity titres in the 244 DI virus-treated and infected group and the oseltamivir-treated and infected group was not significant. On day 4 the infectivity titre in Cytidine deaminase the 244 DI virus-treated infected group was 6-fold lower than in the oseltamivir-treated infected groups on day 4 (p = 0.04; Fig. 4c). Titres began to fall from day 4 and by day 6 those in the 244

DI virus-treated infected group and the untreated infected group had fallen to 103.4 and 103.3 ffu per ferret, respectively. However, on day 6 the infectivity of the oseltamivir-treated infected group was 123-fold higher than the control infected group (105.4 ffu per ferret), a highly significant difference (p = 0.004; Fig. 4d). All five animals in the oseltamivir treated group had high titres of infectious influenza virus. The possibility that the influenza virus had developed resistance to oseltamivir was investigated by determining if the virus from the oseltamivir-treated infected group had developed the H275Y amino acid change that frequently accompanies resistance to oseltamivir. This was not found and the reason for high infectivity titres and/or slower virus clearance in the presence of oseltamivir is not known. Infectivity in all groups was undetectable by day 8, showing that 244 DI virus did not compromise virus clearance or lead to persistence of virus infectivity.