Authors’ reply. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11

The selection and emergence of the D222G mutation as a cause or consequence of more severe lower respiratory tract infection is still to be resolved. Emergence of this mutant is likely to exacerbate severity of disease, but by itself, may be neither necessary nor sufficient to account for a severe disease outcome, which is invariably a balance between virus virulence factors and host immune response capability. Further work is needed, both at the level of reductionist experimental pathology work in the animal model, and at the observational level in human populations.