Posted on 01/06/2008 6:19:08 PM PST by blam
Key To Avian Flu In Humans Discovered
ScienceDaily (Jan. 7, 2008) — MIT researchers have uncovered a critical difference between flu viruses that infect birds and humans, a discovery that could help scientists monitor the evolution of avian flu strains and aid in the development of vaccines against a deadly flu pandemic.
This transmission electron micrograph (TEM), taken at a magnification of 150,000x, revealed the ultrastructural details of an avian influenza A (H5N1) virion, a type of bird flu virus which is a subtype of avian influenza A. At this magnification, one may note the stippled appearance of the roughened surface of the proteinaceous coat encasing the virion. (Credit: CDC/Cynthia Goldsmith/ Jackie Katz)
The researchers found that a virus's ability to infect humans depends on whether it can bind to one specific shape of receptor on the surface of human respiratory cells.
"Now that we know what to look for, this could help us not only monitor the bird flu virus, but it can aid in the development of potentially improved therapeutic interventions for both avian and seasonal flu," said Ram Sasisekharan, MIT Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology, and the senior author of a paper on the work that will appear in the Jan. 6 issue of Nature Biotechnology.
Flu viruses come in many strains, and not all of them can infect humans. Strains known as H1 or H3 have "jumped" from birds to humans and hence are tailored to attack cells of the human upper respiratory tract. H5 strains are usually confined to birds, but when they do infect humans they can have very high fatality rates.
In the past decade, isolated outbreaks of avian flu (H5N1) in humans have raised concerns that a deadly pandemic could arise if the avian flu evolves to a form that can easily infect humans and pass from person to person. Some scientists believe such an outbreak could rival the 1918 "Spanish flu" that killed 50 million to 100 million people worldwide.
Scientists already knew that whether an influenza virus infects humans depends on whether its hemagglutinin, a protein found on the virus surface, can bind to sugar (or glycan) receptors in the respiratory tract. Human respiratory cells have glycan receptors classified as alpha 2-6; avian respiratory cells' glycan receptors are known as alpha 2-3. This classification is based on how the sugars are linked together when they are displayed on cells.
Until now, scientists had believed that a genetic switch that allows the virus to bind to alpha 2-6 receptors instead of alpha 2-3 receptors is responsible for avian viruses' ability to jump to humans.
The MIT study shows that that view does not adequately explain how viruses evolve to infect humans. The new work reveals that, more specifically, it is the ability of a flu virus to bind to a certain shape, or topology, of specific alpha 2-6 glycan receptor that determines whether it will infect humans.
Alpha 2-6 glycan receptors come in two shapes-one that resembles an umbrella, and another that resembles a cone. The MIT team found that to infect humans, flu viruses must bind to the umbrella-shaped alpha 2-6 receptor.
Thus, Sasisekharan and his team have redefined the host receptor for influenza and the criteria for how H5N1 can jump to humans. They did so by showing that the shape of the sugars-and not the type of linkage-is the key determinant for human adaptation of these deadly viruses.
This new interpretation explains inconsistencies that plagued the previous model, according to Sasisekharan. For example, some flu strains that can bind to alpha 2-6 receptors do not infect humans very well. It turns out that those viruses bind to cone-shaped alpha 2-6 receptors, which are present in the human respiratory tract but in much smaller numbers than umbrella-shaped alpha 2-6 receptors.
This new paradigm should help researchers develop a better way to track the evolution of avian flu leading to human adaptation, Sasisekharan said. Now, they know to look for avian viruses that have evolved the ability to bind to umbrella-shaped alpha 2-6 receptors.
That knowledge could help them create vaccines tailored to combat a potential pandemic. Similarly, these findings will help in the development of more effective strategies for seasonal flu, which still is a leading cause of death.
"Subtle changes in influenza viruses over time can dramatically influence the likelihood that these viruses will be able to infect human populations, and this is a huge concern," said Jeremy Berg, director of the National Institute for General Medical Sciences, which funded the research. "This work enables researchers to look at flu viruses in an entirely new way. Dr. Sasisekharan's team achieved this through a multifaceted approach that combines laboratory experiments with the 'mining' of NIH-supported databases, leading to new insights into how the flu virus can adapt to a human host."
Other authors of the Nature Biotechnology paper are Terrence Tumpey of the Centers for Disease Control and Prevention; Aarthi Chandrasekaran, graduate student in MIT's Department of Biological Engineering (BE); Aravind Srinivasan and Karthik Viswanathan, postdoctoral associates in BE; Rahul Raman, research scientist in BE; S. Raguram, visiting scientist in BE; and Viswanathan Sasisekharan, visiting scientist in the Harvard-MIT Division of Health Sciences and Technology.
Adapted from materials provided by Massachusetts Institute of Technology.
BF Ping.
b_sharp, doc30, smokin Joe -- *PING*!
real science, real results. (Virology)
Junk science, junk results. (Global Warming)
What a bunch of spoil sports. They’ve been doing a Chicken Little for 10 years that the bird flu will kill us all, and moping because it hasn’t.
Yup
This is research you can sink your teeth into
The Flu virus is a seasonal pestilence
Information like this may make the seasonal misery
(and sometimes mortality) of the Flu
A thing in the past, like smallpox
The science here is simply amazing.
Ping! (Thanks, blam!)
Thanks for the ping!
So, are places where avian flu is now endemic, checking and publishing the changes and types of H5N1 viruses? How will we know if/when the virus evolves to more easily infect humans? Is WHO doing it? USAMRIID? The CDC?
Will they tell the world immediately if they discover a high rate of dangerous changes?
Just askin...
Scientists discover new key to flu transmission
*************************EXCERPT****************************
By Julie Steenhuysen
CHICAGO (Reuters) - Flu viruses must be able to pick a very specific type of lock before entering human respiratory cells, U.S. researchers said on Sunday, offering a new understanding of how flu viruses work.
The discovery may help scientists better monitor changes in the H5N1 bird flu virus that could trigger a deadly pandemic in humans. And it may lead to better ways to fight it, they said.
The scientists found that a flu virus must be able to attach itself to an umbrella-shaped receptor coating human respiratory cells before it can infect cells in the upper airways.
"What the lock needs is the right key. It opens the door," said Ram Sasisekharan, a professor of biological engineering and health sciences at Massachusetts Institute of Technology in Cambridge.
The H5N1 avian flu virus now almost exclusively infects birds. But it can occasionally pass to a person.
Experts have feared that the bird flu virus would evolve slightly into a form that people can easily catch and pass to one another, triggering an epidemic.
"We now know what to look for," said Sasisekharan, whose study appears in the journal Nature Biotechnology.
Before a flu virus can enter a human respiratory cell, a protein on the surface of the virus must bind with chains of sugars called glycans that sit on the outside of the cells.
Checking, but disclosure may be less forthcoming. I would monitor every data source available, and not just the official ones which have to wait for lab confirmation in order to release a statement (otherwise they can be accused of not doing good science).
One complicating factor is that of who gets to develop and market vaccines, and that is apparently limiting the distribution of samples.
There are other political/economic considerations as well, (especially with the Olympics coming up in Beijing), and the lurking concept that if one nation can develop a vaccine and limit its distribution to its own people or even just selected groups within that subset, then a lot of undesireables can be eliminated, and the possibility of conquest of neighbors and reallocation of natural resources becomes manifest as well.
I saw that last night.
Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin
Supplementary information This is a normal HTML link to the pdf link for the supplementary information of Chandrasekaran, A. et al.
I had to restart my computer after I tried to open the pdf link for the supplementary information. It does open when the number of windows that are open are not too many.
Well said, Joe, and I agree.
neverdem, the H5N1 virus is continually changing. Eventually, it will make a change that bypasses the current human defense against it.
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