Amino acid determinants conferring stable sialidase activity at low pH for H5N1 influenza A virus neuraminidase

Avian influenza A viruses (IAVs) and human 1918, 1957, and 1968 pandemic IAVs all have neuraminidases (NAs) that are stable at low pH sialidase activity, yet most human epidemic IAVs do not. We examined the pH stability of H5N1 highly pathogenic avian IAV (HPAI) NAs and identified amino acids responsible for conferring stability at low pH. We found that, unlike other avian viruses, most H5N1 IAVs isolated since 2003 had NAs that were unstable at low pH, similar to human epidemic IAVs. These H5N1 viruses are thus already human virus-like and, therefore, have the frequent infections of humans.

▸ All neuraminidases (NAs) of avian influenza A viruses (IAVs) are stable at low pH. ▸ Human 1918, 1957, and 1968 pandemic IAVs also have NAs that are stable at low pH. ▸ Most human epidemic IAVs have NAs that are unstable at low pH. ▸ The NAs of most H5N1 IAVs isolated since 2003 are unstable at low pH. ▸ Instability of H5N1 IAV NAs at low pH might explain frequent human infections.