Washington29 PB2 Virulence Factor Domain, Mixed Signal at residue 703 Matches Shanghai71T from May

Segment 1 (PB2) of the previously deposited TamiFlu Resistant Washington29 specimen was entered this evening at GenBank with a mixed signal at residue 703, downstream from a recognised Virulence Factor at 701.

We have seen movement at those residues within ΣPF11^* previously in a very important Chinese sequence.  The May 31 version of A/Shanghai/71T carried the following PF11 PB2 Polymorphisms including Virulence Factors¹.

• E627K
• D678N
• D680N
• D701N
• R703K

Considerable laboratory effort continued with this Chinese specimen due to the Trait-Enhancing nature of the E627K genetic acquisition.  The first Shanghai71T sub-clone also carried E627K; whereas, the second sub-clonal version published on 2009-06-24 of Shanghai71T reversed all but the 703K.

We have also noted variance within ΣPF11 and potential donor candidates in the adjacent upstream area to the Palese lab's PB2 Virulence Domain.  Movement at residues coding for amino acids 674T and 677G are noted in particular and may require additional study to determine trait correlation. 

674T features on a Hong Kong swine (HKswNS1659), a lab virulent Puerto Rico8 variant (LabVir_hvPF8), the last two previous Seasonal H1N1 reservoirs and is found in conjunction with 627K, the Seasonal NA Quadruple Combination (106I, 248N, 275Y, 286G) and TamiFlu Resistance on the 2009 H1N1 Seasonal specimen A/Shanghai/LWS1.  677G is found on the PF11 background throughout Europe and the US Eastern seaboard, but more importantly is in conjunction with 627K on 2006 and 2007 Indonesian H5N1 specimens.

The TamiFlu Resistant Washington29 sequence in the United States acquiring PB2 material in and around this recognised PB2 Virulence Domain begins to build a formidable virus.

1. Steel J, Lowen AC, Mubareka S, Palese P (2009) Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N. PLoS Pathog 5(1): e1000252. doi:10.1371/journal.ppat.1000252

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H5N1 Polymorphism, Q296H, Arises in Singapore, World’s Busiest Port

A review of HA:296 is in order based on today’s releases.

The polymorphism, Q296H, was found in the 11 year old female death in SaoPaulo43812, is widely conserved in the Northeastern US, is conserved in Italy and is found in Northwestern Europe.

This change has moved into Singapore, a major gateway to the world. Singapore shares the title of Busiest Port in the World with Shanghai in different categories. 296H emerged in Singapore in one of the four sequences sampled on 2009-06-14 and deposited yesterday, A/Singapore/TLL54. No other segments for this sample are on file for review.

SingaporeTLL54

• 2E
• 35I
• 66E
• 296H 

The Glutamate (E) near the beginning matches 1918 and most H5N1. This HA homology additionally occurs with SaoPaulo2233, Italy127 and NY4197, each of which also share 296H with this SingaporeTLL54 specimen under review.

The 296H change is rare on PF11 sequences in Asia with only 2 matches in China (Shanghai143T, Shandong1) and 1 in Japan (Tokushima1).  On the PF11 background, only 31 sequences across the globe now carry 296H.

New York obviously provides a substantial international vector from the airports and seaports.  Shanghai and Singapore vector air and sea extensively.  The Italian port of Ancona provides a significant trans-Adriatic ferry service.

An intra-segment exclusivity exists presently in PF11 between 296H and 206T though donors are proximal in China, Japan, SaoPaulo, Finland and Canada with extensive coverage in New York and Italy.

We suggest tracking for interplay between 296H and the recent RBD changes noted in QC1 and QC2.

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