These cases could be examples of post infection mutations, or alternatively show the limits in the coverage of sequenced avian strains. High mortality rate markers In a second experiment human influenza strains were separated into two groups: a high mortality rate group containing

pandemic genomes selected from the 1918, 1957 and 1968 outbreaks, human H5N1 and the H1N1 1976 deadly New Jersey infection and a low mortality rate group AZD5363 supplier containing all other whole genome human infection samples. As with the pandemic conserved host type markers, the high mortality rate markers were required to be positively identified in each of the sequenced strains associated with the three pandemic outbreaks (e.g. perfect conservation and no ambiguous sequence codes). Eighteen of 2,112 sequenced human influenza genomes (9 of 286 when samples

were grouped Bafilomycin A1 cell line by year, subtype and location) not in the high mortality rate class contained all 18 of the identified high mortality rate markers. These cases occurred in H2N2 and H3N2 strains from the 1960s and 1970s in years following their respective pandemics. Figure2shows the high mortality rate genotypes among the sequenced samples with minimum 1% frequency for the three host categories. The figure shows that the human high mortality rate genotype is the most common avian genotype and that each avian strain has at least 13 of the 18 high mortality rate markers. Analogous to the co-variation pattern found in GSK872 concentration the NS segment for the human host type markers, the non-lethal human strains show that where the hemagglutinin (HA), neuraminidase (NA) subtype lacks the high mortality rate makers (rank 27, 29 and 31 in Figure2) Thymidylate synthase high mortality rate markers are found in other segments. The opposite also occurs (rank 26, 28 and 30 in Figure2). Figure 2 High mortality

rate genotypes. Each genotype is specified by a column in the table, where the bars above the column reflect relative frequency in the sequenced genomes. V (green) means the genotype has the virulent consensus for the position, and N means non-virulent consensus. Bars above each table column mark the relative frequency for avian (red), human – both high mortality rate and low mortality rate cases (blue) and non-avian non-human strains (orange bars). The most common non-human non-avian genotype (rank 43 in Figure2) is a swine H1N1, which shares many of the high mortality rate variants but misses the mutations found on the NS and PB1 segments. The second most common subtype shares all but one of the high mortality rate variants and is circulating in horse (rank 15) but Figure1shows that H3N8 lacks most of the human host type markers (rank 19 and 21 in Figure1). The complete high mortality rate variant (rank 0) are H5N1 cases that infect a broad host range including swine, tiger, domestic cat, civet, and stone marten.