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

TL;DR

This study investigates the punctuated evolution of influenza virus hemagglutinin (HA) under opposing migration and vaccination pressures, revealing abrupt changes called proteinquakes linked to hydropathic shifts affecting virus replication.

Contribution

It uncovers the complex, punctuated evolution of HA, demonstrating how hydropathic shifts and proteinquakes influence influenza virus adaptation and balance between receptor-binding and destruction activities.

Findings

HA exhibits abrupt proteinquakes linked to hydropathic shifts.

HA evolution shows punctuated changes correlated with NA mutations.

Hydropathic analysis can monitor influenza evolution over decades.

Abstract

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 sialic acid interactions are required for optimal balance between the receptor-binding and receptor-destroying activities of HA and NA for efficient virus replication. Our comprehensive results present an historical (1945-2011) panorama of HA evolution over thousands of strains, and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains. While the common influenza virus discussed here has been rendered almost harmless by decades of vaccination programs, the sequential decoding lessons learned here are applicable to other viruses that are emerging as powerful weapons for controlling and even curing common organ cancers. Those engineered oncolytic drugs will be discussed in future papers.