Why is it that animal viruses seem to be responsible for virtually every modern plague—West Nile, Ebola, AIDS, SARS, and most recently, the frightening (but so far contained) outbreak of bird flu in Southeast Asia? Biologists from London’s Medical Research Council are trying to find the answer—by looking at the past.
Team leader Sir John Skehel and his colleagues set their sights on the 1918 influenza virus, preserved in human bodies buried in the Alaskan permafrost. They were particularly interested in the virus’s molecular engineering because the 1918 “Spanish flu” was the most deadly pandemic in history, killing 20 million to 40 million worldwide. So the researchers illuminated virus surface proteins with X-rays to reveal their structure, a technique known as X-ray crystallography.
Scientists used to believe the virus jumped to humans after incubating in pigs, which can be infected by both bird and human viruses. But the London researchers have shown a few small changes in the shape of a surface protein were all it took to enable the bird version of Spanish flu to bind onto human cells. Such molecular binding is what permits human-to-human transmission and is the first step toward a deadly epidemic. The changes are so small that a bird flu could mutate directly into one that targets humans.
“This finding still doesn’t explain why one strain kills more than another,” Skehel says. “But it does tell us what is required of a virus to spread to humans.” Because the necessary transformations seem so small, Skehel worries that many as yet unidentified animal viruses already have the ability to jump into humans. Further structural analysis of surface proteins may be the key to understanding and treating emerging viruses when they take that leap.
