Hierarchical hydropathic evolution of influenza glycoproteins (N2, H3, A/H3N2) under relentless vaccination pressure

TL;DR

This study uses hydropathic analysis to investigate the evolutionary patterns of influenza glycoproteins H3 and N2 under vaccination pressure, revealing hierarchical trends that extend phylogenetic insights and have potential therapeutic applications.

Contribution

It introduces a hierarchical hydropathic approach to analyze influenza glycoprotein evolution, distinguishing vaccination effects from migration influences and linking these trends across multiple scales.

Findings

N2 evolution is primarily driven by vaccination pressure.

H1 and H3 evolutions involve complex migration and vaccination interactions.

Hydropathic trends align with and extend phylogenetic results.

Abstract

Hemagglutinin (HA) and neuraminidase (NA) are highly variable envelope glycoproteins. Here hydropathic analysis, previously applied to quantify common flu (H1N1) evolution (1934-), is applied to the evolution of less common but more virulent (avian derived) H3N2 (1968-), beginning with N2. Whereas N1 exhibited opposing migration and vaccination pressures, the dominant N2 trend is due to vaccination, with only secondary migration interactions. Separation and evaluation of these effects is made possible by the use of two distinct hydropathic scales representing first-order and second-order thermodynamic interactions. The evolutions of H1 and H3 are more complex, with larger competing migration and vaccination effects. The linkages of H3 and N2 evolutionary trends are examined on two modular length scales, medium (glycosidic) and large (corresponding to sialic acid interactions). The hierarchical hydropathic results complement and greatly extend advanced phylogenetic results obtained from similarity studies. They exhibit simple quantitative trends that can be transferred to engineer oncolytic properties of other viral proteins to treat recalcitrant cancers.