[2008] US and Japanese researchers crack flu pandemic's deadly code:

http://www.theaustralian.news.com.au/story/0,25197,24854588-30417,00.html

Leigh Dayton, Science writer | December 30, 2008
Article from:  The Australian

THE genetic code that made the 1918 killer flu so deadly has finally been cracked, claim US and Japanese researchers, who say their discovery may lead to new drugs able to keep future outbreaks in check.

By experimenting with genetic material recovered from preserved lung tissues of three victims of the so-called Spanish influenza, a team led by virologist Yoshihiro Kawaoka claim the virus landed a lethal one-two punch.

First it disrupted normal immune reactions, as previously known. But then it infected its victims' lungs with deadly consequences. Ordinary flu bugs infect just the nose and throat. Potentially dangerous lung infections are caused secondarily by bacteria.

"People have been trying to sort out for some time what it is about the 1918 influenza that made it so nasty,'' said Sydney-based medical virologist Dominic Dwyer with Westmead Hospital's Institute for Clinical Pathology and Medical Research.

"What this study shows is, in fact, it's a combination of a number of genes that made the strain so virulent,'' he said.

According to virologist and infectious diseases physican Steve Wesselingh, dean of medicine at Monash University in Melbourne, the final step is to tease out just how the virus killed its victims after spreading to their lungs.

Weilding this multi-gene weapon the 1918 virus infected roughly 500 million people, or 30 per cent of the world's population.

Worse, it killed an estimated 20-50 million people, over 2.5 per cent of those infected, compared with less than 0.1 per cent killed during other influenza epidemics.

The genetic key to the invasion consists of three genes which code for a part of the virus called it's RNA polymerase complex, Professor Kawaoka's group reported yesterday in the US journal Proceedings of the National Academy of Sciences.

Professor Kawaoka is with the University of Wisconsin-Madison, as well as Japan's Kobe and Tokyo Universities where his colleagues are based.

Professor Kawaoka and his team started with all eight of the virus's genetic segments, which other scientists had pulled from the preserved lung tissues and multiplied many-fold. Next, they created hybrid viruses, half 1918-half current flu bugs.

Finally, the scientists infected ferrets _ who suffer flu most like people _ to see how each hybrid acted. Their experiments revealed that the key genes were those which over-stimulated the animals' immune system and infected their lungs. Those genes could be "targets'' for improved flu drugs, they reported.