Then, they sent the bacteria containing the viral gene sequences to Tumpey, who inserted them into the cells to produce the virus.
The researchers also produced variations of the virus for comparison, with certain Spanish flu genes replaced by the corresponding genes from other flu viruses. Then they studied the viruses' effects in mice, chick embryos and human lung cells and identified the constellation of genes that was responsible for the Spanish flu virus' extreme virulence.
One gene associated with high virulence was the HA gene, which encodes the hemagglutinin surface protein that helps the virus attach to cells and replicate properly. This gene seemed to be responsible for much of the severe lung damage reported in people infected with the Spanish flu. The three genes encoding the viral "polymerase" enzymes, which form the virus' basic replication machinery, were also found to be important for high virulence.
"Given that HA is responsible for so much pathology in the lung, if we could identify the mechanism for how that happens and then block it, perhaps it would be useful for antiviral development. With the identification of the polymerase genes contributing to disease, that represents another set of genes that might also be a good target for prophylactic and therapeutic interventions," Tumpey said.
Although more research needs to be done on antivirals and vaccines for a future flu pandemic, Tumpey noted some encouraging signs. The FDA-approved flu antiviral drugs, oseltamivir and amantadine, have been shown to be effective against viruses carrying certain genes from the Spanish flu virus. And, vaccines containing the Spanish flu HA gene, as well as another gene from this virus, were protective in mice.