The last century has seen two major pandemics caused by
the H1N1 virus—the Spanish flu in 1918 and the swine flu scare of 2009, which
had thousands traveling with surgical masks and clamoring for vaccination. But
scientists did not know what distinguished the swine flu from ordinary
influenza in pigs or seasonal outbreaks in humans, giving it the power to
travel extensively and infect large populations.
Until now. Prof. Nir Ben-Tal of Tel Aviv University’s Department of Biochemistry and Molecular
Biology and his graduate student Daphna Meroz, in collaboration with Dr. Tomer
Hertz of Seattle’s Fred Hutchinson
Cancer Research
Center, have developed a
unique computational method to address this question. Published in the journal PNAS, the research presents a valuable
tool for identifying viral mutation strategies, tracking various virus strains,
and developing vaccinations and antivirals which can protect the population. It
may also lead to more precisely designed vaccines to combat these viral
mutations.
Their
method reveals that mutations in the virus’ amino acids in specific positions,
such as antigenic receptor sites, may explain how the new strain successfully
spread throughout the population in 2009. These alterations allowed the strain
to evade both existing vaccines and the immune system’s defenses.
Playing a game of cat and mouse
Viruses and our immune systems are constantly at war. A virus constantly
mutates to escape notice, and our immune system strives to play catch-up—to
recognize the virus and mobilize the body’s defense system.
To
determine the spread of the 2009 human pandemic flu, Ben-Tal and his
fellow researchers analyzed the hemagglutinin protein, which controls the
virus’ ability to fuse to a host cell in the body and transfer the genome which
contains the information needed to make more virus. Eventually, he says, our
immune system is able to recognize a virus’ hemagglutinin, which triggers its
reaction to fight against the virus.
Using
a statistical learning algorithm, the researchers compared amino acid positions
in the 2009 strain of H1N1 against the common flu and the strain of H1N1 found
in swine flu, and discovered that major sequence changes that had occurred,
altering antigenic sites and severely compromising the immune system’s ability
to recognize and react to the virus.
“Our
new computation method showed that the main differences between the pandemic
strain and the common seasonal H1N1 strain are in some 10 amino acid
positions,” Ben-Tal and Meroz report. “That’s all it
takes.”
Experiments
conducted by Sun-Woo Yoon, Mariette F. Ducatez, and Thomas P. Fabrizio from
Prof. Richard J. Webby’s lab at St. Jude Children’s Research
Hospital in Memphis, Tenn.,
confirmed some of the theoretical predictions.
Predicting pandemic
Like its 1918 predecessor the Spanish flu, the 2009 pandemic flu will likely go
into “hibernation”—now that this particular strain has been
recognized by the immune system, its power to infect has been compromised. But
we were lucky: despite the relatively low death toll of the pandemic in 2009,
similar to the number of deaths attributable to common seasonal flu, we might
be facing more dangerous future outbreaks of mutated H1N1 varieties.
Because
of the enormous mutation rate, says Ben-Tal, viruses can spread widely and
rapidly, and vaccines are fairly inefficient. In the future, a refined version
of this computational method may ultimately be used to generically compare
various strains of viruses. This in-depth analysis might lead to the ability to
predict how a strain will morph and determine if a pandemic could strike.
This is an important step towards
revealing the amino acid determinants of the emergence of flu pandemics, but
there is more work to be done, the researchers say.
Filed Under: Drug Discovery
