3.3 In vitro inhibitory effects of aprotinin on infections caused by oseltamivir-resistant influenza A and B viruses
We next examined the inhibitory effects of aprotinin against an oseltamivir-resistant IAV (A/Bris/10/07; H3N2). As shown in Fig. 4A, A/Bris/10/07 (H3N2) virus was less susceptible to oseltamivir. Our genetic analysis revealed that the H28T mutation in HA conferred the reduced susceptibility of the H3N2 virus to oseltamivir (data not shown). However, aprotinin could effectively reduce the production of the H3N2 virus (Fig. 5A).
IBVs are generally less susceptible to oseltamivir than IAVs.[21,22] Therefore, we here investigated the inhibitory effects of aprotinin on influenza B virus (B/Seoul/32/2011) infection. As shown in Fig. 5B, the IBV was around 50- to 100-fold less susceptible to oseltamivir. However, aprotinin was more effective than oseltamivir at reducing IBV production.
Taken together, these results suggest that aprotinin can significantly reduce the production of oseltamivir-resistant IAV and of IBV, which is less susceptible to oseltamivir.