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Hemagglutinin (HA) and neuraminidase (NA) are highly variable envelopeglycoproteins. Here hydropathic analysis, previously applied to quantify commonflu (H1N1) evolution (1934-), is applied to the evolution of less common butmore virulent (avian derived) H3N2 (1968-), beginning with N2. Whereas N1exhibited opposing migration and vaccination pressures, the dominant N2 trendis due to vaccination, with only secondary migration interactions. Separationand evaluation of these effects is made possible by the use of two distincthydropathic scales representing first-order and second-order thermodynamicinteractions. The evolutions of H1 and H3 are more complex, with largercompeting migration and vaccination effects. The linkages of H3 and N2evolutionary trends are examined on two modular length scales, medium(glycosidic) and large (corresponding to sialic acid interactions). Thehierarchical hydropathic results complement and greatly extend advancedphylogenetic results obtained from similarity studies. They exhibit simplequantitative trends that can be transferred to engineer oncolytic properties ofother viral proteins to treat recalcitrant cancers.

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