  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.
