OK, what does this mean?
I mean it. Very confused about the findings AND implications.
“H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects1, 2. Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-2,6-galactose (SA2,6Gal), whereas the latter prefer those ending in SA2,3Gal (refs 3–6). A conversion from SA2,3Gal to SA2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor-binding haemagglutinin (HA) molecule that would enable avian H5N1 viruses to recognize human-type host cell receptors, it may be possible to predict (and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.”
link:http://www.nature.com/nature/journal/v444/n7117/abs/nature05264.html
Grace RN – at 11:08
It means that in some of the existing circulating strains H5N1 have acquired mutations that allow them to live higher up in your throat instead of way down in the lungs. That is because it has a sequence that allows it to live at a lower temp (34C) instead of the warm temps (higher “core” body temps) and it can attach to the sugars in the throat and upper lungs (mucus = those polysaccharides) instead of the sugars lining the lower lungs.
It also means we were very lucky in Egypt, Turkey and Iraq since some H5N1 seen there have the mutation but we stopped before it could spread and pick up more human binding mutations.
In addition, it means that its sequences now share longer sequences with circulating strains including the ever-present type B flu. The longer the sequences the faster it can “mate” (hydrogen bond to the RNA sequences) and the faster it can now pick up more human binding regions. And that can all be done without effect the regions that give it the large CFR’s.
None of that is good.
Excuse me I am no MD nor do I play one on TV. I will now go crawl under a rock and play dumb and let others correct my misunderstandings.
Oh yes, being higher in the lungs/throat means it is easier to cough or sneeze the stuff up. That leads to faster spread (higher R0)if it doesn’t kill to quickly.
Commentary
Recombinomics Commentary November 15, 2006
two of these changes, lysine at position 182 and arginine at position 192, were present in the HA’s of clade-2 H5N1 viruses isolated from two individuals in Azerbaijan and one individual in Iraq,clade
“The above comments from today’s Nature paper describe patients infected with the Qinghai strain of H5N1. The paper identified acquisitions in human H5N1 isolates that enhanced binding to human receptors, either individually or in combination.
The above comment is somewhat ambiguous. It is not clear if all three patients had both receptor bind domain (RBD) changes described above, or both changes were found among the three patients. The statement cannot be independently confirmed, because the sequences from these patients are still being hoarded by WHO, and have not been made public.
The hoarding of the sequences by WHO, weakens their complaints about China not sharing samples or sequences, when WHO and consultants at St Jude, Hong Kong University, and Weybridge are hoarding thousands of H5N1 sequence collected this year, including human cases as indicated above.
The hoarding labs have failed to understand how these changes are acquired and continue to call them random mutations.”
Long story short
One interpretation of Dr. Niman’s commentary regarding the Nature article is, a great deal of information continues to be withheld from the public and other scientists by China & WHO. Without the facts we’ll never get a handle on the evolution of the various viral clades and sub-clades. Weapons of Mass Confusion, continue to serve political/commercial interests.
Sound familiar?
“host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-2,6-galactose (SA2,6Gal), whereas the latter prefer those ending in SA2,3Gal”
Can’t recall where I saw this, but, don’t human, (and other mammals) have both these kinds in the epithelial layer of the respiratory tract? Even if humans don’t have as many “avian” receptors?
Recognizing human receptors just underlines “still looking like no chance of pandemic going away”? I’d think all too soon they’ll have to stop worrying about potential, and start dealing with fallout from actual pandemic. Just don’t think humans are going to get their collective acts together to start making vaccines that will hit a moving target; systems are too fragile for that. Sure hope I’m wrong.
Dennis C.
OK, thanks.
So is the implication=this season’s flu bug could perhaps meet H5N1 in some exotic corner of the planet and go…where no one wants it go ie efficient H2H?
The song remains the same.
Grace RN – at 11:30 some exotic corner …go ie efficient H2H
That is what it looks like to me. It has all the pieces now. They just all have to come together in one place. And that place could be a single person- exotic or not. It just needs to do a few H2H cycles without being “contained” and it is good as there.
I think I will sign off for a while and order some more powdered eggs, tea, and books.
you can get the Nature article here:
http://tinyurl.com/y5l5w8 but it costs $30.
You can read the abstract for free.
There is a summary of the paper and discussions in the H5N1 Receptor Binding 2 thread. Let’s move discussion over there so we don’t have duplicate threads. Thanks!
I’m going to copy the posts over there so they are all in one place.
I think the barrier between human and animal has now been breached too many times. The protection it once offered us seems to be in question with the zoonotics. You could read the report that the chickens have adapted better than the humans, and that infulenza B in the future won’t be referred to as mild.