Deaths in Brasil Match 1918 and H5N1 Receptor Binding Domain at HA 225G

Within 9 Sao Paulo sequences released today from Brasil spanning late July to mid August 2009, we find at least 6 distinct HA backgrounds of which 5 are compelling and 2 are novel to the PF11 reservoir.  Sequences from potentially expired patients are indicated boldly.  This level of genetic diversity at key antigen sites on the Hemagglutinin (HA/H1) in a single geography during a common timeframe is of great interest and, at a minimum, reflects regional Acquisition Acceleration. 

Bear in mind that in the early stages of the pandemic, PF11 exhibited extreme stability demonstrating 100% homology across entire countries.  You will find in the early record several groups of more than 400 HA and NA sequences across diverse geography that match exactly.  We are now in a new phase as the PF11 reservoir has been passaged within humans through one winter cycle in the Southern Hemisphere and has demonstrated the ability to rapidly gain beneficial genetic traits, traits that drive toward fatal outcomes.

Background1
SaoPaulo53823
2E
188I
296H

The presumably fatal case appears to be the first instance of 188I on a PF11 background.  Human-fit Seasonal Influenza from 2007, 2008 and 2009 as well as the 2001 HKswNS1569 carry 188I, including ShanghaiLWS1 with the M230I RBD polymorphism.  Movement at 188 to Asparagine (N) has occured in NY3502, Utsunomiya01 and Utsunomiya02.

Background2
SaoPaulo53838
2E
225N
296H

Background3
SaoPaulo57831
2E
296H

Backgrounds1, 2 & 3 continue the PF11 Intra-Segment exclusivity of 206T and 296H though proximal donors of 206T are available.

Background4
SaoPaulo53845
206T
225N

In addition to these two specimens from Brasil, 225N is found only on one other PF11 sequence, NY4099.  Several Korean swine carry the change.  More importantly, a linked candidate, A/swine/Hong Kong/NS1659/2001, featuring widely in PF11 Genetic Acquisition paths also carries 225N.  HKswNS1659 shows HA:188I, 189T, 252M & 261K with additional matching to the 2008-2009 Seasonal Influenza NA Triple Combination, 106I, 248N, 286G.

Background5
SaoPaulo53206, SaoPaulo53225
206T
225G

Receptor Binding Domain changes at 225 may be correlative to fatal outcomes in Brasil as 100% of these cases appear to have expired (4/4).  However, the RBD change may not be a requirement for fatality in SaoPaulo.  Of three cases carrying only the 206T revision, one (SaoPaulo54392) appears to have expired.

225G is consensus for H5N1, is carried on NewYork1918 and only appears in six other PF11 sequences across the US and Mexico.

MX3955
MXInDRE4114
NY04
GA01
TX05
TX11

225X is demonstrated several times in the US proximal to 225G in area and time.

NY11
NY31
TX10
CA13
NE02

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