Punctuated evolution of influenza virus hemagglutinin (A/H1N1) under opposing migration and vaccination pressures

Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Previously we identified much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. We showed that these smaller changes can be monitored very accurately across many Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages, which increases gradually due to migration, but decreases abruptly under large-scale vaccination pressures. Here we show that, while HA evolution is much more complex, it still shows abrupt punctuation changes linked to those of NA. HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions. HA proteinquakes based on