Characteristics of Influenza HA-NA Interdependence Determined Through a Graphical Technique
Using novel graphical techniques and hypothesizing a coupling between the HA and NA, we devised a coupling factor to estimate the interdependence, if any, between HA and NA sequences covering a global sample of 10 subtypes and 164 sequences. We found that (a) the coupling we hypothesized between HAs and NAs is characteristic of each subtype, (b) within each subtype the coupling value is significantly different for human infecting strains and those that infect avians, and (c) artificial strains made up by mixing and matching HAs and NAs from different subtypes produce coupling factors that are far from the characteristic values for the parent subtype indicating possibly non-viable viruses, a result that matches with experimental evidence of Zhang et al. . We also show that some natural strains that did not fit the characteristic values for its subtype could have been possible mismatches during viral packaging. Our observations have important consequences for drug and vaccine design and for monitoring of influenza virus reassortments and possible evolution of human pandemics.
Keywords: Drug and vaccine development; HA sequence plots; HA-NA coupling characteristics; HA-NA interdependence; NA sequence plots; graphical representation; mathematical characterization; monitoring flu sequences
Document Type: Research Article
Publication date: December 1, 2014
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