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MIT Finds Key To Avian Flu In Humans
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.
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 appeared 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.
http://www.mit.edu
MIT Gãseºte cheia de la gripa aviarã la om - MIT Finds Key To Avian Flu In Humans - articole medicale engleza - startsanatate