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PUBLIC HEALTH | May 02, 2009

Flu Forensics

Avian flu research sheds light on swine flu outbreak.
“This is similar to the method by which the current swine influenza strain likely formed. The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus.”

 

A study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu pandemic is greater than previously thought. Results of the study, published in Proceedings of the National Academy of Sciences, also illustrate how the current swine flu outbreak likely came about. As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However Associate Professor Daniel Perez from the University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.
 
“This is similar to the method by which the current swine influenza strain likely formed,” says Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project. “The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing.”
 
In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together, Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface avian flu genes from the H9N2 virus. Though it comes from a different strain of avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez says his research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.
 
Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.
 
When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, the researchers concluded that after an animal-human hybrid influenza virus forms in nature, a human pandemic of this virus is potentially just a few mutations away.
 
“We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets,” Perez says. “We will be doing more research on the current swine flu strain to study its specific genetic mutations.”

 

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