Overall, the human infections of avian origin have acquired no more than a few human specific markers, which suggests that avian strains are not rapidly Selleck PD-1/PD-L1 inhibitor acquiring human persistent markers through genetic drift. The high mortality rate markers are ubiquitous in the avian background and are distinct from the vast majority of human infections. While the host type markers clearly separate avian and human strains, there are a number of cases where LY2835219 descendants of the 1957 and 1968 pandemics continued to retain all of the predicted high mortality rate markers. Finding that classification accuracy for high mortality rate

strains is lower than the host type classification weakens support for the notion of a single essential common set of high mortality rate markers. The reduced classification accuracy comes primarily from the fact that the H2N2 sequences continue

to maintain the 18 markers into the 1960s, well past the associated pandemic. Thus, these 18 markers do not clearly distinguish between pandemic and non-pandemic associated H2N2 strains. Instead the results support the AZD8186 molecular weight hypothesis that additional factors play an important role in determining the mortality rates of a specific strain. This highlights the potential importance to pandemic potential of host immunity and antigenic novelty. Even in the case of host type markers where classification accuracy is very high, markers could be missed. For example, the HA and NA genes play a critical role in host specific infection, but this study focused specifically on the persistent markers, and host specificity markers were found only on the more heavily conserved internal proteins. Additional PLEK2 potentially important host type markers that are not persistent should still exist. It is worth noting that 5 of the 18 high mortality rate markers lie on the NA or PB1 segments implying that they were independently introduced into the three respective pandemic outbreaks [7]. Aside from the 18 high mortality rate markers persisting in H2N2 strains past the 1957 pandemic time frame, the markers give an overall high degree of classification

accuracy and, therefore, a potentially useful common, although not sufficient, set of associated genetic factors. Among the high mortality rate strains not associated with a pandemic, only the 1976 H1N1 isolate lacks all 18 markers (4 are not present). Because the 1976 sample is a small contributor to the total number of high mortality rate features, it does not significantly contribute to the classification model. Substituting a single alternate 1976 swine strain for example, would have limited impact on the markers chosen unless more strains were added or a single strain was given the same weight as the pandemic strains in which perfect conservation is required. In this case mixing low mortality rate strains into the high mortality rate class would substantially alter the reported set of persistent markers.