|Home||Founder||What's New||In The News||Consulting|
Paradigm Shift Intervention Monitoring
The Health Protection Agency (HPA)
recently released four sets of pH1N1 sequences from the UK. The
most recent isolate, A/England/4880374/2010, was collected November 28,
2010 and had S188T
along with additional
HA markers seen in earlier isolates from Thailand, India,
Australia, New Zealand, and Ghana. The above change is adjacent
to the receptor binding domain position 190, and changes flanking this
position were associated with the fixing of
H274Y in seasonal H1N1.
In addition to HA sequences, many of the earlier isolates from this sub-clade had public NA and MP sequences, which had additional shared markers confirming that this sub-clade was spreading via clonal expansion and may be under positive selection.
However, one of the NA markers associated with this sub-clade, N368K, was present in another isolate from the UK, A/England/3220137/2010, which was collected in August (see list here). This isolate did not have the other NA and MP markers linked to the S188T sub-clade, indicating the N368K was acquired via recombination.
Support for recombination was also seen in the PB2 sequence. Although the PB2 sequences of these two UK isolates are readily distinguish by a series of synonymous markers, both sequences have two non-synonymous changes, which match, V344M (see list here) and I354L (see list here). The matching of both non-synonymous markers by two UK isolates provides strong additional evidence for recombination.
Similar evidence is present for another UK isolate, A/England/4780352/2010, which has recombined HA markers circulating in Australia, including, D100N, which is present in trH1N1 sequences from the United States (see list here).
Recombination drives rapid evolution, and the UK recombinants raise concerns that the shuffling of these polymorphisms has generated more virulent pH1N1 that can also evade immunity generated by infections of vaccinations last season.