TAU researchers discover clues to predict flu epidemic

Until now, scientists were in the dark about what distinguishes the “swine flu” from the ordinary type in pigs or seasonal outbreaks in humans.

Swine flu patient  (photo credit: Ariel Jerzolomiski)
Swine flu patient
(photo credit: Ariel Jerzolomiski)
The H1N1 influenza virus usually causes limited infection, but it occasionally turns virulent and kills throughout the world.
Until now, scientists were in the dark about what distinguishes the “swine flu” from the ordinary type in pigs or seasonal outbreaks in humans – as in 1918 and 2009 – giving it the power to travel extensively and infect large populations.
Prof. Nir Ben-Tal of Tel Aviv University’s biochemistry and molecular biology department 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.
They just published their research, which constitutes a valuable tool for identifying viral mutation strategies, tracking various virus strains and developing vaccinations and protective anti-virals. It appeared this week in the prestigious American journal Proceedings of the National Academy of Science. They suggest their work may also lead to more precisely designed vaccines to combat these viral mutations.
Their method reveals that mutations in the virus’s amino acids in specific positions may explain how the new strain successfully spread throughout the population in 2009, in which more than 18,000 died around the world. These alterations allowed the strain to evade both existing vaccines and the immune system’s defenses.
“Viruses and our immune systems are constantly at war,” said Ben-Tal. A virus constantly mutates to escape notice, and our immune system strives to play catch-up and recognize the virus to mobilize the body’s immune system.
To determine the spread of the 2009 flu, Ben-Tal and his colleagues analyzed the hemagglutinin protein, which controls the virus’s ability to fuse to a host cell in the body and transfer the genome, which contains the information needed to make more viruses. Eventually, he says, our immune system is able to recognize a virus’s hemagglutinin, which triggers its reaction to fight the virus.
Using a statistical algorithm, the researchers compared amino acid positions in the 2009 strain of H1N1 against the common flu and the strain of H1N1 found in the type affecting pigs. They discovered major sequence changes 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 the main differences between the pandemic strain and the common seasonal H1N1 strain are in about 10 amino acid positions,” Ben-Tal and Meroz reported. “That’s all it takes.”
Experiments conducted at St. Jude Children’s Research Hospital in Memphis, Tennessee confirmed some of the theoretical predictions.
The scientists believe that like the 1918 Spanish flu, which is estimated to have killed at least 50 million people, 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, 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.