Thursday, December 22, 2011

pH1N1: Avian Homology on High Diversity Sequences Distinguished Across Globe

Avian Homology on High Diversity Sequences Distinguished Across Globe

On 2011-12-20, the UK National Institute of Medical Research released a group of human pH1N1 sequences at GISAID including 46 full HA and 45 full NA segments. The sample dates cover 2010-12-15 to 2011-08-11 (44 during 2011). Fifteen originating labs provided the samples though no specification of clinical outcome is notated within the NIMR deposit.

The volume and span of the deposit demonstrates the ongoing significant rate of genetic acquisition onto 4 of the established clades, alongside several uncladed sequences. Four sequences carry clade-defining elements from multiple clades. Ambiguity in the traces is high with 44 mixed traces. This deposit brings the first pH1N1 sequence with a combined 40 polymorphisms (HA and NA) on the highly avian-influenced, SenegalDakar14_1x_2011_04_14 (HA 29 / NA 11) [EPI346724]. A certain population of geographically-dispersed sequences shows a combined HA and NA total of 25 or more revisions (10 sequences, 22% of the deposit).

Enhanced acquisition of avian genetic data and convergence of polymorphisms found on high-CFR and high-zoonotic pH1N1 strains are quantified. Variant clades appear to be gaining data from the same sources as the pH1N1 HA 230I strains and the Upsilon series of 84 sequences (5.33% CFR).

Five countries (Cameroon, France, England, Iceland and Hungary) produced a subset of 9 sequences bearing 12 polymorphisms within the aa156-aa159 range, a domain documented to produce Vaccine Escape. Hungary7_xM_2011_01_31 (HA 11 / NA 06) [EPI346709] on Clade2: 188T with RBS 226R (Vaccine Match) applies polymorphic behaviour at 3 consecutive Vaccine Escape locations in this domain (HA 157E mix wt, 158E mix wt and 159D mix wt).

One sequence is TamiFlu Resistant with NA 275Y. More importantly a strong gravity is indicated in the polymorphic pattern suggestive that more TmX due to NA 247N will be seen in the future on these types of strains. Considering the HA and NA distinct polymorphic supersets on these human pandemic sequences, 36 changes (10%) appear on earlier pandemic sequences with TmX due to NA 247N and 81 changes (23%) appear on the subset of H5N1 sequences that carry the NA 247N marker.

Evaluating the 226 distinct HA changes derived from these 46 human pandemic sequences against fractional HA subsets of several animal serotypes, a minimum of 72% share homology. Avian H1N1 leads the match count at 115 polymorphic positions while H6N1 continues to participate at a significant level (79 matches). Homology to Avian H9N2 (62), H13 (52) and the High-CFR H5N1 (50) demonstrates that this pandemic has ample opportunity for genetic input from the extant reservoirs to amplify clinical conditions.

Though the zoonotic serotype backgrounds profiled against these human polymorphisms are entirely variant, these many codon-level homologies crossing multiple zoonotic reservoirs into the human pandemic illuminates the GeneWurx premise that the origin of the human H1N1 pandemic be reconsidered as avian.

One TamiFlu Resistant sequence (NA 275Y) features on a Clade2: 188T background and carries HA RBS 227G with the HA 158E (mixture with wild type) that has repeatedly been observed to promote Vaccine Escape.

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