Posted on 02/19/2008 10:17:10 AM PST by blam
Spread Of 1918 Flu Pandemic Explained
This transmission electron micrograph of an ultra-thin specimen revealed some of the ultra-structural morphologic features seen in 1918 influenza virus virions. The prominent surface projections on the virions are composed of either the hemagglutinin, or neuraminidase type of glycoproteins. (Credit: Cynthia Goldsmith)
ScienceDaily (Feb. 19, 2008) — MIT researchers have explained why two mutations in the H1N1 avian flu virus were critical for viral transmission in humans during the 1918 pandemic outbreak that killed at least 50 million people.
The team showed that the 1918 influenza strain developed two mutations in a surface molecule called hemagglutinin (HA), which allowed it to bind tightly to receptors in the human upper respiratory tract.
"Two mutations dramatically change the HA binding affinity to receptors found in the human upper airways," said Ram Sasisekharan, the Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology.
Sasisekharan is the senior author of a paper on the work to be published in the Feb. 18 issue of the Proceedings of the National Academy of Sciences. In January, Sasisekharan and colleagues reported in Nature Biotechnology that flu viruses can only bind to human respiratory cells if they match the shape of sugar (or glycan) receptors found on those cells.
The glycan receptors found in the human respiratory tract are known as alpha 2-6 receptors, and they come in two shapes-one resembling an open umbrella, and another resembling a cone. To infect humans the MIT team found that avian flu viruses must gain the ability to bind to the umbrella-shaped alpha 2-6 receptor.
In the current study, the team discovered that two mutations in HA allow flu viruses to bind tightly or with high affinity to the umbrella-shaped glycan receptors.
"The affinity between the influenza virus HA and the glycan receptors appears to be a critical determinant for viral transmission," said Sasisekharan.
The researchers used the 1918 influenza virus as a model system to investigate the biochemical basis for hemagglutinin binding to glycans, which leads to viral transmission. They compared the virus that caused the 1918 pandemic (known as SC18) with a strain called NY18 that differs from SC18 by only one amino acid, and also the AV18 strain, which differs from SC18 by two amino acids.
Using ferrets (which are susceptible to human flu strains), researchers had earlier found that, while SC18 transmitted efficiently between ferrets, NY18 is only slightly infectious and AV18 not at all infectious.
These earlier findings correlate with the viruses' ability to bind umbrella-shaped alpha 2-6 glycan receptors, demonstrated in the current PNAS study.
NY18, which is only slightly infectious, binds to the umbrella-shaped alpha 2-6 receptors but not as well as SC18, which is highly infectious. AV18, which does not infect humans, does not have any affinity for the umbrella-shaped alpha 2-6 receptors and binds only to alpha 2-3 receptors.
Another strain, TX18, binds to alpha 2-6 and alpha 2-3 but is much more infectious than NY18, because it binds with high affinity to the umbrella-shaped alpha 2-6 receptors.
Researchers from the Centers for Disease Control and Prevention reported on the varying infectiousness of these strains last year, but the PNAS study is the first that explains the exact biochemical reason underlying these differences.
This new work could aid researchers in monitoring the HA mutations in the H5N1 avian flu strains currently circulating in Asia. These mutations could enable the virus to jump from birds to humans, as many epidemiologists fear will occur.
Other authors of the PNAS paper are Aravind Srinivasan and Karthik Viswanathan, postdoctoral associates in MIT's Department of Biological Engineering (BE); Rahul Raman, research scientist in BE; Aarthi Chandrasekaran, graduate student in BE; S. Raguram, visiting scientist in BE; Viswanathan Sasisekharan, visiting scientist in the Harvard-MIT Division of Health Sciences and Technology, and Terrence Tumpey of the Centers for Disease Control and Prevention.
The research was funded by the National Institute of General Medical Sciences and the Singapore-MIT Alliance for Research and Technology (SMART).
Adapted from materials provided by Massachusetts Institute of Technology.
BF Ping.
I hate when that happens.
Ping! (thanks, blam!)
Pandemics on average come every 24 years and we are overdue. Some are widespread but still mild. This is a serious threat because of the urbanization of masses and frequent travel patterns of probable hosts.
What’s the explanation for the 1918 flu appearing all over the world at the same time?
I’m curious, assuming they didn’t have electron microscopes in 1918, are these photos of a virus LIKE the 1918 case or are they photos of the resurrected stuff?
From what I have read, they removed the virus from people buried in an area that had perma-frost, so the virus has remained in “cold-storage” effectively.
Scientists.
Doncha just love em?
Maybe a Freeper(ette) with better knowledge on this can fill us in.
And now so does everyone else.
Lock and key stuff. When we really get a decent handle on predicting protein folding we’ll be able to kill everybody on earth. I mean that in the nicest possible way.
We know how to weaponize Avian flu
Huh? these mutations occurred spontaneously, what do you mean weaponize Avian flu?
We know how to weaponize Avian flu
Huh? these mutations occurred spontaneously, what do you mean weaponize Avian flu?
Bump
As hypothesized by Paul W. Ewald in his book, Plague Time, the spread seems more likely to have been an artifact of human actions, not only overcrowding in military hospitals and barracks, but also the worldwide failure of civilian authorities to appreciate the need for isolating/quarantining the ill.
(Ewald's logic involves an application of evolutionary theory that's too detailed for me to attempt a summary. But if you're seriously interested in the topic, I think you can't go wrong by reading his short book!)
I believe it traveled rapidly around the globe several times before tapering off. That’s the impression I got from “The Great Influenza.”
ping
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