Showing posts with label Shanghai71T. Show all posts
Showing posts with label Shanghai71T. Show all posts

2009-09-29

E627K from July Discovered Retrospectively, Tied to Netherland's Vacation Island in Diabetic Patient and Adolescent Female

Though the sequences have not been released, the team at Erasmus MC in Rotterdam has done us all a great service by providing an early report of 627K in the Netherlands. 

The multiple cases all vector from visits to a popular vacation island between July 13 and August 9.  Two of the cases do not appear to be related via direct contact, potentially indicating an endemic and silent spread of a minor PF11 population carrying the human-fit virulence factor 627K in a sub-clade that may match the major circulating sub-clade there but for the Lysine recombination.  Ten of twelve (83%) sample specimens from this geography fall into this sub-clade indicating the potential for dominant circulation in that area.

As this release of information via Promed is very limited, additional evalution and insight will require amendment and revision to this article as the matter is clarified on several accounts, including specification of the E627K sequence count and the various ratios confirming the certain Hydra Effect demonstrated in the study population.

In our reading, 3 distinct cases are described in the Osterhaus release. The researchers may have mentioned “two patients” because the family contact and the younger sister may have been directly evaluated by them in a clinical setting?

  • Male Diabetic who may have shared activities with ill female camper, onset 2009-08-09
  • Female camper, onset after returning home 2009-07-20  
  • Female family contact of ill camper, onset after camper returned on 2009-07-20
  • Younger sister of female family contact, onset 2009-07-23

This highly interpretive post is preliminary based on inconclusive language in the press release.

No mention is made of the correlating PB2 virulence mediators 701N and 703K at this time in the information released.  We suspect these to be absent due to the non-fatal clinical outcomes; however, confirmation would be useful.

As the samples were examined retrospectively, little new observational evidence will be forthcoming.  Rational projections due to this 627K mid-Summer emergence in the Netherlands and the late May emergence in Shanghai71T could cause us to expect a geographically-dispersed, wild-type sub-population carrying this virulence factor.

Tenacious sub-clonal evaluation of current sequences in the United States will likely indicate mixed peaks at the PB2 residue coding for the Lysine at 627.


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2009-09-10

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/LWS1677G 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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