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Commentary
WHO Evades Ukraine
Sequence Questions at News Conference
Recombinomics
Commentary 12:23
November 15, 2009
Phil Serafino, Bloomberg: Dr Shindo........I have a second question also which may not be your area of expertise but have you heard anything about the mutation of the virus or has it changed at all - are we looking at anything different than a few months ago.
Dr Shindo: Well, I can answer that question first. The virus is quite stable. It hasn't changed........
Joseph: This is Joseph from Kuala Lumpur - I am from the Sun Media......I just want to ask whether or not any slight mutation even a drift variant has been noticed so far.
Dr Shindo: Amazingly this virus is very stable and part of the reason, virologists (are saying) is because of the lack of pre-existing immunity in population so that virus doesn't have to mutate to escape from people's immunity. So it's quite stable.
The above comments are from the WHO update on Thursday, announcing new recommendations on the use of anti-virals to treat pandemic H1N1. The two questions above are by reporters who were looking for comment on small changes in H1N1 in general, and Ukraine sequences in particular. A week earlier Keiji Fukuda made some general comments about the sequences, noting that final analysis would "probably take a couple of days" but in general there were no "big mutations". However, "big mutations" just refers to reassortment, and there have been no examples of big mutations due to reassortment in any recent sequences. All sequences reported thus far have the same original constellation of flu genes, one human, PB1; two avian (PA and PB2); and seven swine (North Americana and Eurasian).
The reporters were asking about "small" mutations, such as drift mutations, or those affecting the receptor binding domain. Sequence changes in the receptor binding domain are already published. One position (225) is of interest because it was associated with the spread and dominance of amantadine resistance (S31N) in seasonal H3N2. That particular change, D225N, has been reported in two pandemic H1N1 sequences from New York, as well as two recent sequences from Sau Paulo, both of which were from necropsy tissue from fatal H1N1 cases. Similarly, the same position changed during the 1918 pandemic to D225G. That change has also been reported from the lungs of two other patients who dies in Sau Paulo. Moreover, a third change at that position (D225E) was seen in the Tamiflu resistant sequence identified in Hong Kong from a San Francisco traveler who had not been treated with Tamiflu. That polymorphism is widespread and frequently reported in patients from Spain. Thus, the questions on small changes in sequences were focused on specific single nucleotide changes, but the answers to the questions were just general comments on the stability of the virus and did not address specific changes in the Ukraine sequences.
The failure of WHO to release the Mill Hill sequences, or to even comment on the presence or absence of such specific changes, raises questions. The delay in release of data or comments has led to wild speculation at conspiracy web sites, which are widely carried over the internet, creating significant confusion among those readers, as well as the general public concerned about the excessive and continuing deaths in Ukraine (see map). These concerns have been heightened by accelerating numbers of H1N1 hospitalizations and deaths throughout the northern hemisphere,
Non-responsive answers on the general stability of the H1N1 will not reduce these concerns.
Release of the Ukraine sequences is long overdue.
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