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Paradigm Shift Intervention Monitoring
The recent spike
in severe and fatal H1N1 cases in the UK has raised concerns that
the H1N1 in circulation has evolved into a more virulent form.
The WHO update
on UK noted that there were changes in UK sequences that had been seen
elsewhere, raising concerns that the H1N1 that had been circulating in
Australia had migrated to the UK.
Many of the Australian sequences represented a new sub-clade that was linked to sever cases and vaccine breakthrough. Two HA changes had been cited, N142D (N126D in H3 numbering) and E391K (E375K in H3 numbering), which were thought to be involved in the immunological escape and more severe cases.
The Health Protection Agency recently released four HA sequences from cases in the UK. E375K is widespread and present in three of the UK sequences, A/England/4880374/2010, A/England/4780352/2010, A/England/3220137/2010 (see list here). In addition, A/England/4780352/2010 had N126D, confirming that these changes were appearing in the UK (see list here). However, analysis of the S188T sub-clade indicated A/England/4880374/2010 was recombining with A/England/3220137/2010 in the NA and PB2 gene segments.
Moreover, A/England/4780352/2010 had another HA change, D100N, which was also present in Australia (see list here), but was not on the same series of isolates that had N126D, indicating it had been appended onto the background with N126D via recombination. In addition, D100N was present in H1N1 triple reassortants (trH1N1) found in US patients prior to the start of the 2009 pandemic.
Thus, A/England/4780352/2010 is a recombinant with polymorphisms co-circulating in Australia, but on separate sub-clades. The combining of these genetic changes produces a novel sequence, which may play a role in the spike of severe and fatal cases in the UK.
Release of December sequence from such cases would help in determining the involvement of these recombinants in the activity being reported in the UK.