Genetic sequencing and recreation of the virus that caused the 1918 Spanish flu pandemic may enable the world to track influenza viruses before they can arouse a new pandemic, a US virologist said on Wednesday.
The new knowledge of the 1918 flu virus' genetic sequences will be "extremely helpful in determining the events that may lead to the adaptation of avian viruses to humans," said Robert Belshe, a professor at the St. Louis University.
In a preview article in the Nov. 24 issue of the New England Journal of Medicine, Belshe said that scientists have known at least two mechanisms by which a flu pandemic could emerge.
The first, Belshe wrote, is a direct spread and adaption of an entirely avian virus from birds to humans. This is what happened during the 1918 Spanish flu, the deadliest of last century's three pandemics.
And the second is a "reassortment" virus that mixes bird flu with already circulating human influenza strains to create a new strain. This was the case during the flu pandemics in 1957 and 1968.
Both mechanisms were observed during worldwide pandemics of the 20th century, and scientists now believe that the prospect of a new flu pandemic during this century could involve either of these two possibilities.
And the H5N1 virus strain now circulating in Asian and European countries may evolve in similar ways. Based on the knowledge of the 1918 virus, an H1N1 strain, scientists have found 10 critical amino acids for the virus to adapt to humans, Belshe said.
All avian flue viruses can transmit from fowl to humans sporadically, but what is new with the H5N1 strain, is the broadening of the range of avian and nonavian species that have become infected, he said.
By comparing the consensus sequence of the three avian influenza polymerase genes PA, PB1, and PB2 with the 1918 sequence, as well as with more contemporary influenza viruses, scientists have identified four amino acids of PA, one of PB1, and five of PB2 that are found in human influenza viruses (including the 1918 virus) but generally not in avian influenza viruses.
"In two instances, these amino acids are found in nuclear localization signaling regions, suggesting that some or all of these amino acid differences are critical for the virus to adapt to humans," the article said.
"The role of PB1 must be critical, since in both 1957 and 1968, this polymerase gene was transferred along with the hemagglutinin during reassortment."
Moreover, the genetic sequences of the H5N1 virus reveal that several human isolates of these viruses contain one of the five amino acid changes in PB2 that have been identified as important to the ability of the 1918 virus to infect humans, according to Belshe.
"This finding suggests that several additional genetic changes must occur before these viruses will begin to spread efficiently from person to person," he wrote in the article.
And as the virus continues to adapt, scientists now know what to look for. Belshe said scientists should conduct worldwide surveillance to monitor this adaptation process.
"The genetic sequences of avian viruses may provide a window through which to monitor these sporadic transmissions for the potential of the viruses to adapt to humans."
"The occurrence of additional genetic changes in the H5N1 virus circulating in birds that match the consensus sequence for PA, PB1, or PB2 in human influenza would be cause for heightened concern."
"It gives us some reassurance that by continuing to monitor the current virus in birds, we can get a sense as to when it'll be an efficient virus," Belshe said. "We may have some time to develop new vaccines and better therapies."