Scientists Find Key In Virus
Switch From Birds To Humans
From Patricia Doyle, PhD

Hello Jeff: The work below, i.e. how the virus infects birds and humans etc: is that of Dr. Don C. Wiley. It was one of his last projects, if not, the last one before his death.
The British researchers used x-ray crystallography to determine the three-dimensional structure of the haemagglutinin.
Mystery Of 1918 Flu Pandemic Solved
Scientists Identify Key Factor In Switch From Birds To Humans
By Tim Radford
Science Editor
The Guardian - UK
British scientists have solved a secret of an avian flu virus which killed up to 40 million people worldwide 86 years ago. They now know more about how a disease of birds switched to humans to trigger the most lethal outbreak in history.
A team from the National Institute for Medical Research at Mill Hill, north London, used pathological samples taken from victims of the Spanish influenza pandemic of 1918 to recreate the structure of a haemagglutinin protein vital in the leap between species.
"This tells us more about the transmission from birds to humans," said Sir John Skehel, leader of the team.
"However, it will not have an immediate impact on the situation currently unfolding in the far east with the chicken flu known as H5 since, from our previous work, we know that the 1918 and H5 haemagglutinins are quite different."
The research is published in the online edition of the US journal Science today. It is backed up by a study from the Scripps Research Institute in La Jolla, California.
Viruses smuggle themselves into a host cell to replicate and then spread infection. Haemagglutinin is a spike-like molecule on the surface of the virus which sticks to receptors on the cells of birds or humans.
The teams worked with DNA preserved in the Alaskan permafrost and in preserved tissue taken from young American soldiers who died in 1918.
The British researchers used x-ray crystallography to determine the three-dimensional structure of the haemagglutinin.
The American team started from a different point and studied the precursor protein that becomes haemagglutinin.
Between them, they have thrown light on one of history's great puzzles. Flu kills thousands of Britons every year but those most at risk are the elderly, the very young or those suffering from some other illness.
But the 1918 strain was different: it hit the young, healthy and well nourished of neutral countries as fiercely as it ravaged the refugee camps in wartorn Europe.
It first appeared in March 1918 in a military camp in Kansas, in the US, and 522 soldiers were ill within two days. In the end it killed about 700,000 people in the US and about 230,000 in Britain. The French called it la grippe, the Russians, "the Spanish lady". Mortality rates were huge: in some communities up to 70% died. The virus disappeared within 18 months as mysteriously as it came, leaving 20-40 million dead.
Flu is a disease of birds as well as humans and other mammals. The virus was first found at Mill Hill in 1933, in a ferret. The infection mutates swiftly, with new strains appearing almost every year.
The latest research is not likely to lead to better drugs or vaccines, but it will help researchers and could pay off in more effective surveillance of successive variations in the virus.
The British researchers also looked at haemagglutinin structures from two viruses isolated just after the 1918 pandemic, one from swine, one from humans.There have been several lethal pandemics since 1918, including the Asian flu outbreak of 1957 and Hong Kong flu in 1968.
Sir John said: "Bird viruses recognise different receptors than human viruses. So when they transfer into the human population they have got to change their binding capacity. With the Asian flu and Hong Kong flu in 1957 and 1968, we think we know how they do that.
"But in the case of the 1918-1957 viruses, where the Asian and Hong Kong flu changed, these ones stayed the same: they looked just like the avian progenitor. So the mystery is: what happened to allow them to infect humans?"
Guardian Unlimited © Guardian Newspapers Limited 2004,14207,1142137,00.html



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