Printer-friendly format

Virologists and other scientists are always keeping an eye on influenza viruses in order to detect which ones represent the risk of becoming pandemic.

Fears were raised in 2005 when the H5N1 avian flu rapidly spread in birds across Asia and into Europe. That alarming trend spurred research into creating new vaccines and keeping a very close watch on the virus.

Scientists at St. Jude Children’s Research Hospital published a report in September in the online edition of the Journal of Virology detailing key features that distinguish influenza viruses found in birds and those found in humans. In 2006, St. Jude researchers sequenced more than 200 bird flu viruses and defined all the amino acids and nucleotides in the entire genetic sequence. According to St. Jude literature, scientists used the information from that sequence and a mathematical technique to identify specific amino acid building blocks that are statistically more likely to appear in avian influenza virus proteins and those that are more likely to be human. The differences in these amino acids can be used as markers for tracking changes in H5N1 avian flu strains that threaten humans.

“It wasn’t surprising once we finally sorted through the data to find the differences between bird flu viruses and human flu viruses that the H5N1 was still mostly bird, and that was very reassuring” said David Finkelstein, PhD, a research associate at the St. Jude Hartwell Center for Bioinformatics and Biotechnology. “That doesn’t mean that it won’t someday become more humanized, and if it was, of course it would be very dangerous.”

To get a sense of where on that pathway things might become dangerous, the research team examined the last dangerous pandemic viruses that came from birds, which include the 1918, 1957 and 1968 pandemics. Descendents of the 1957 and 1968 influenza strains eventually became similar to today’s typical seasonal flu rather than deadly pandemics. But the 1918 flu, the deadliest pandemic known, was neither bird or human; it was right in the middle. It was one of the most dangerous influenza viruses ever seen, not just because it had a high rate of death, but a high rate of transmissibility from human to human.

This survey data defined 32 different locations in proteins that indicate where a gene mutation caused the existing amino acid to be substituted with a different amino acid. Any one of these 32 positions can reveal with 95 percent accuracy whether a scientist is looking at a bird or human flu.

The researchers discovered these markers by computationally surveying the sequence of amino acids in 10,671 proteins from avian influenza viruses and 13,757 proteins from human flu viruses. The survey identified these 32 persistent markers in five bird and human virus proteins.

The 1918 pandemic virus had only 13 of the 32 markers. Those 13 were highlighted as much more likely to be crucial for a transmissibility set, or crossover mutation from bird to human.

“The first and most obvious thing is that we have a highly variable avian group compared to this relatively consistent, less variable human group,” explained Finkelstein. “Not all avian [influenza viruses] can make it into human beings. There is a restriction that goes on. So obviously, medically, you do care quite a bit about which ones could [cross over] and where the danger is.”

For some reason, birds are able to accept a wider range of flu viruses than humans. Researchers have identified more than 90 variants of flu in birds compared to only five in humans. Some flu strains are harmful in birds but most are completely innocuous. The H5N1 is unusual in that it kills it’s host.

Finkelstein said while this mathematical evidence for these markers is compelling, it will take functional lab tests to validate the findings. “It’s something that people can actually test in a lab one by one,” said Finkelstein. “It allows people to monitor, relatively quickly, new arising strains of H5N1.”

The fortunate news is that the H5N1 hasn’t changed from when it started.

“That doesn’t mean that it couldn’t do it in a relatively short period of time,” Finkelstein cautioned. “And the risk is still there.”

It hasn’t gotten any worse, but scientists don’t have a sense of if and when it could get worse.

“If it hasn’t shown signs of changing very quickly, this means it’s probably going to be a little slower in arriving, if it’s going to change,” he added. “We may have a few more years. The more time the better.”



October 2007

Tags:

None

Login and voice your opinion!