Swine Flu Update
by ilene - January 12th, 2010 12:32 am
By Ilene
Previous series of swine flu updates by me here.
Transmission of Fatal H1N1 D225G/N Accelerates Concerns
Courtesy of Dr. Henry Niman, Recombinomics Commentary
Recently released H1N1 HA sequences have significantly accelerated pandemic concerns. These sequences have either D225G, D225N, or both and produce a case fatality rate at or near 100% in many countries….
By the 100% fatality rate, Dr. Niman means that they are finding these changes in the tested fatal cases in some countries. Keep in mind, these are small numbers of cases. It does not mean that all cases with these changes prove fatal. It might be more clear to say a large portion of the fatal cases show these changes in the infecting viruses.
[the] transmission and expansion of these fatal sequences in eastern Europe, including Russia have increased concerns, as has the "low reactor" status as determined by Mill Hill for a tested Ukraine sequence.
Some of the earliest sequences with D225G were in the United States last spring and were generally mild. However, initial cases in the US were generally mild, which may have reflected low viral loads infecting a naïve population…
"Low reactors" status means that the virus is not triggering the immune response expected due to changes in the structure of certain viral proteins (here, the influenza hemagglutinin proteins). Immune responses target specific proteins and the target proteins’ structure is critical to the immune response. Not all changes in a protein will greatly reduce its immunogenicity (ability to stimulate the immune response) but certain changes will. The change from the wild-type (common) HA protein to the HA protein with the D225G marker appears to have this adverse effect--i.e., the altered viruses will not provoke the stronger immune response generated in response to the wild-type virus and/or the swine flu vaccine.
These observations are cause for concern, not alarm. The changes in the H1N1 virus are natural and predictable; Dr. Niman predicted these changes would occur.
There already was interest in position 225 for a number of reasons. D225N was in seasonal H3N2 and linked to the fixing [establishment of widespread] of adamantine resistance (S31N), while D225G was in 1918 and 1919 samples and linked to a change in receptor binding domain specificities which would target subsets of cells in the lung. In addition, the polymorphism [genetic change] was jumping from one genetic background to
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Flu News
by ilene - January 5th, 2010 10:32 pm
Here’s the latest by Dr. Henry Niman. I’ve made a few helpful comments in red. – Ilene
D225E and D225N H1N1 RBD Changes in Turkey
Courtesy of Henry Niman, PhD
Recombinomics Commentary
January 5, 2010
The Refik Saydam National Public Health Agency has released 29 HA [hemagglutinin] sequences from Ankara, Turkey. Several were partial sequences, but 26 covered the receptor binding domain and 8 had D225E,… while one had D225N,…
My comment: D225 is the most common or wild-type receptor binding protein - the hemagglutinin (HA) protein – which enables the virus to bind to tissues in the respiratory tract of infected people.
A change in the amino acid in position 225 of the receptor binding domain (RBD) is symbolized by using the letter representing the new amino acid, e.g. "G" for glycine in "D225G." The marker D225G signifies that a glycine (G) is present in the 225 position, replacing the amino acid usually in this position, aspartic acid, or D (hence the wild-type marker is "D225"). Glutamic acid, E, and asparagine, N, are two other amino acids that have been found in this position in non-wild-type swine flu viruses.
The change in the receptor binding protein from D to G alters the protein’s preference for binding to human tissues. Viruses with the D225G marker bind in the lung tissue, rather than binding in the upper respiratory tract (nasal area and throat), the more typical target. This appears to result in more severe disesase which may trigger a "cytokine storm" reaction in the lungs. Whether substitution with "E" or "N" causes similar changes is not known. Theoretically, if the immune response is generated against the wild-type protein D225, viruses with D225G, D225E or D225N markers might avoid the immune system’s response.
[Back to Dr. Niman] The outcomes of these patients were not given but media reports have described a rapid in increase in H1N1 fatalities in Turkey. A large number of HA sequences with D225E has been published from Spain, and recently released GISAID sequences from Sweden and the UK also have D225E, including three fatal cases from Sweden. The prior reports of D225G and D225N associations with fatal cases has raised concerns that changes at position 225 could alter tissue tropism or aid in immune escape, leading to more severe and fatal cases.
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H1N1 Update
by ilene - December 30th, 2009 11:27 am
H1N1 Update: Watching and Waiting
by Ilene with guest expert Dr. Henry Niman at Recombinomics
Watching and Waiting
Although the numbers of new cases of swine flu have been declining in many regions, including the United States, it is too early to know whether or not there will be subsequent waves of disease.
"Based on my experience with new diseases and the lessons learned from past pandemics, I think we should remain cautious and observe the evolution of the pandemic over the next six to 12 months before declaring victory," World Health Organization Director General Margaret Chan tells Swiss newspaper Le Temps. (World Health Official Says Swine Flu Still a Threat)
Although the WHO is taking a cautious approach, changes in the virus’s genome that increase its virulence and resistance to Tamiflu are becoming more common. Dr. Henry Niman, expert in flu virus evolution, believes another wave of flu illnesses will occur in early 2010. In addition, he believes resistance to Tamiflu will become "fixed," similarly to how this genetic change evolved in the seasonal H1N1 virus. (See Flu Update: Tamiflu resistance and Ukraine update, and Efficacy of Roche’s Flu Drug Tamiflu In Doubt, by David Phillips.)
WHO: H1N1 swine flu pandemic will stick around for another year
The World Health Organization warned government health authorities to remain vigilant on the H1N1 swine flu pandemic, saying the virus could mutate before vaccines can help it dissipate.
The World Health Organization is confident that the H1N1 swine flu pandemic will be under control in a year’s time – however, WHO officials warned global governments to remain vigilant for any mutations in the troublesome bug.
Dr. Niman believes this wave will be more severe than the previous two--but not due to random mutations. Rather, this will result from the process of recombination. Due to recombination, increasingly greater transmission of aggressive variants (D225G, D225E and D225N) and Tamiflu-resistant viruses will occur.
Ukraine
I’ve reprinted two recent articles at Recombinomics, with my comments in blue.
The WHO Surprise on D225G / D225N H1N1 Fatalities, Recombinomics Commentary
After considering the current available virological, epidemiological and clinical findings and following discussions on an earlier draft with WHO and its European-based Collaborating Centre ECDC has come to a preliminary formulation namely that the G222D/N
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Philip R. Davis is a founder Phil's Stock World, a stock and options trading site that teaches the art of options trading to newcomers and devises advanced strategies for expert traders...
Ilene is editor and affiliate program
coordinator for PSW.
