In both recent seasonal H1N1 strains and in H5N1 highly pathogenic viruses, mutations that increase the NA activity, protein stability or cell surface transport likely compensate for the effects of the mutation at 275 that would otherwise decrease the function of the enzyme. 8, 9, 14, 15 Examples of such mutations are D344N, 9 and V235M and/or R223Q. 14 Neither of Brookes et al. the latter two mutations currently exist in the NA protein of pH1N1 isolates, but further circulation of the pH1N1 virus in humans may select for these or other NA or haemagglutinin (HA) mutations that better prime the virus to accommodate or even select for the H275Y mutation.