Biology News from millerandlevine.com

To best understand the material in this web article, read the sections in our textbook that explain how the immune system works. (Dragonfly book Sections 40-1 and 40-2; Elephant book sections 45-1 and 45-2.)

Even as experts wrestle with the yearly challenges of making the next vaccine, they are always, in the backs of their minds, worrying about "the next big one" — a killer flu whose coat proteins are so radically different form existing strains that they could take the immune systems of the entire world's human population by surprise. How do such major variants appear? Where do they come from?

The names of several of the 20^th century's worst flues offer some clues. In 1957, there was the Asian flu. Then, in 1968, there was the Hong Kong flu ­ which infected 50 million Americans and left 70,000 dead in little more than six weeks. Then there was the Shanghai flu. Then the Taiwan flu. Now think. Where have recent reports of bird flu come from? Mainland China. Tawian. Thailand. Vietnam. Do you see a pattern?

But why should so many particularly dangerous strains originate in Asia? And what does this have to do with current fears about the new Asian strains of avian flu? The answer, according to one fascinating hypothesis, is hinted at by the name of yet another nasty strain: "swine flu."

Until a few decades ago, the difference between deadly flu strains and ordinary flu strains was a mystery. But when the Hong Kong flu hit in 1968, new molecular tools enabled researchers to study its genes and proteins. When the Hong Kong strains were compared them with other influenza strains, the results were surprising. Several coat proteins on the Hong Kong strain looked remarkably like proteins isolated from a ducks strain. In fact, the Hong Kong strain carried six protein-coding genes from normal human flu strains, and two genes form a duck strain. Similar analyses were performed on virus samples preserved from the 1957 epidemic. Sure enough, the deadly Asian Flu had carried five genes from human strains and three from avian strains.

Researchers believe that the deadly Hong Kong virus that circulated in 1997 (strain H5N1) was carried genes that originated in three separate strains of avian influenza. Current evidence indicates that these strains came form quail, geese, and teal from mainland China.

Yet all previous experiments had shown that pure avian flu strains either failed to survive and reproduce in humans, or hung on for a couple of days and then disappeared. But if avian strains didn't live in humans, and if human strains didn¹t infect ducks, how did some strains end up with genes from both groups? And how did those "bird flu" strains "learn" to infect humans?

According to one strong hypothesis originated and championed by Robert Webster of St Jude's Hospital in Memphis TN, the answer lives in farmyards. Webster noted that both human and avian flu strains can infect pigs at the same time. And when that occurs, the door is opened to gene-swapping between strains. How?  If virus particles from both human and avian strains infect a single cell of a pig at the same time, their genomes can get mixed up and recombined as viral genes are copied and assembled into new virus particles. At least some of the resulting new viruses appear to contain a deadly combination of traits. They carry enough human-strain genes to enable them to infect people readily. But they also contain coat proteins from duck strains that make them look completely new to human immune systems. And that makes them doubly dangerous.

This schematic illustrates Webster's hypothesis that human and avian influenza strains can both infect pigs — where genes form different strains can be mixed.

Which brings us back to the question of why these nasty strains often emerge in Asia. As you probably know, many Asian countries are very densely populated, and depend on intensive agriculture. In rural areas, animals are raised very differently than they are in the United States. In many places, farmers raise chickens, pigs, and other species in very close association with each other — and with humans. Can you see the connection? In these sorts of situations, birds (which can carry avian flu strains) come into regular close contact with humans (which can carry human flu strains) and pigs (which can often host both avian and human strains). This situation significantly increases the chances of forming a deadly recombinant strain.

Now you can also understand why global officials are so worried about the new bird flu strains in Asia this year. These trains have spread like wildfire among domestic poultry in China, South Korea, Vietnam, Cambodia and Indonesia, Malaysia, Japan, Taiwan, and even as far away as Pakistan. They kill a large percentage of the birds they infect. Meanwhile, some strains in Thailand, Vietnam, and Cambodia occasionally jumped directly from birds to humans — and had killed at least 15 people by the end of January 2004.

So far, this bird flu does not appear to be transferred effectively from one human to another. (The people who have been infected apparently got sick after handling sick birds.) But if one of these strains happens to infect a human who is also infected by a fast-spreading human strain, the result could be a new "killer" flu. And with today'Ws high speed global travel, that strain could spread around the world with lethal speed. So stay tuned for further developments!

Dr. Robert Webster, of St Jude's Hospital in Memphis, TN is one of the world's foremost experts on influenza viruses. His pioneering work has been, and continues to be, of the utmost importance in understanding the emergence and spread of new influenza strains.

This modern poultry farm in South Korea is being closely monitored to check for any signs of infection by avian flu strains

Index of this Web Article:

• Introduction — What's up with the Flu?
• What is influenza — and who gets it?
• Why can we get the flu again and again? And why can't we develop a one-time flu vaccine?
• How are flu vaccines made?
• Why are flu vaccines sometimes not effective?
• Why are researchers so worried about this new bird flu?

Back to Part 5