Hydropathic evolution of hemagglutinin and neuraminidase glycoproteins of A(H1N1 and H3N2) viruses

More virulent strains of influenza virus subtypes H1N1 appeared in 2007 and H3N2 in 2011. The amino acid differences from prior less virulent strains appear to be small when tabulated through sequence alignments and counting site identities and similarities. Here we show how analyzing fractal hydropathic forces responsible for globular compaction and modularity quantifies the mutational origins of increased virulence, and also analyzes receptor sites and N-linked glycan accretion. The two most common influenza A subtypes are H1N1 and H3N2. These viruses are mutation prolific, and their HA (hemagglutinin) and NA (neuraminidase) glycoproteins have evolved in response to migration and vaccination pressures in H1N1 [1,2]. Hydropathic analysis is based on the thermodynamics of the differential geometry of water films that encapsulate globular proteins quite generally. The availability of thousands of mutated amino acid sequences of H1N1 made it an especially attractive subject for fundamental analysis. The emergence of a new H3N2 subtype in 1968 immediately raised the question of how one should characterize the differences between H1N1 and H3N2. Clinical studies in 1985 showed that H3N2 was more severe in all ages and had a higher infection rate in young children than H1N1 [3]. At the molecular level these differences appear to be small when tabulated through sequence alignments and counting site identities and similarities [4]. The appearance of more virulent strains of H1N1 in 2007 and of H3N2 in 2011 raised the even more difficult question of finding HA and NA sequence differences that could be responsible for enhanced virulence. Lurking in the background is the mystery of the extremely virulent 1918 H1N1 pandemic strain, with its peculiar W age mortality profile, different from the normal U profile [5]. This can be