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May 1, 2009 1:26 PM

Seattle immunology expert tapped by NIH for swine flu research

Posted by Kristi Heim

Seattle's global health expertise is being called upon to study the body's immune response to the swine flu virus.

Alan Aderem, co-founder and director of the Institute for Systems Biology, was tapped by the National Institutes of Health (NIH) this week to apply his current research to unlocking the mysteries of the H1N1 "swine flu" virus. Aderem had already received a $20 million NIH grant to study immune response to avian flu.

Aderem and a team of 25 ISB researchers are comparing the swine flu virus with the avian flu virus and the seasonal flu virus. They hope to determine not only how dangerous the current virus could be, but how to treat and prevent it.

The 1918 flu killed millions of people because it produced an overly active immune response. He'll examine proteins in the lung to determine whether the swine flu virus elicits a similar response. I had a conversation with Aderem about his project late Thursday.


Alan Aderem, at work in his Seattle office, specializes in immunology and cell biology.

How did this come about?
Two days ago we had started moving in the direction of applying what we were doing in our big NIH grant to this problem. NIH called this morning and asked specifically to apply what we were doing to this flu, so it was both on our own initiative and NIH.. I won't say commanded but strongly supported us to do this.

How exactly do you study it?
Infect many mice with the virus and then take fluid from the lung. We measure proteins with a very sensitive mass spectrometer and essentially are able to quantify every one of the proteins in the lung. It's important because for a few immune proteins, the way they are secreted is the way the 1918 flu killed the host.

What makes this more serious than seasonal flu?
Usually diseases that are viral or any infectious diseases co-evolved with the host generally are relatively mild. Human flu co-evolved with humans is mild because it's not in the interest of the virus to kill the host. When viruses become very dangerous is when they jump from one species to another. That's why bird flu is so dangerous. Humans have not developed immunity.

Generally speaking bird flu cannot infect humans. There's protein on the surface of bird flu which allows flu to infect a cell that has a very specific protein in the receptor. Human flu has protein that recognizes the human receptor and allows human virus to enter the human cell. The bird virus has a different protein that can't enter humans. But if you have an intermediary like a pig, where human virus can infect it, and bird virus can infect it, when the virus reassembles in the cell, you have more than one type of flu in the cell. It can reassemble and the human gene can go to the bird and vice versa. Now the virus coming out has components of humans, allowing it to infect humans with the bird virus. This virus has some components from bird, some components from pig. Because of that it's a very dangerous. It can get into human cells, has dangerous components from other species and can spread to other humans.

Bird flu is clearly very dangerous. It produces a cytokine storm -- hormone molecules produced by immune cells used to signal other immune cells. If you produce too many, essentially an over exuberance in immune response, that causes severe damage.

What expertise can ISB bring to bear on this problem?
Our main focus is systems biology -- what that does is take global measurements. We measure all of the proteins. We measure all the genes, all the RNA and all the proteins then use very powerful computational tools to understand how the system works holistically.

There are complicated webs of information produced in immune cells when they interact with viruses. One thing we do very well is measure large numbers of proteins very accurately. Those two capacities allow us in this case to examine these immune cells in context of how they respond to flu. how they can compare to other flus and proteins in the lungs and their capacity to do damage.

The idea is they give us the opportunity to find better drug targets and generate more effective vaccines. Drug targets are particularly important because right now Tamiflul is the only drug that's working. One needs to find more targets.

Are people overreacting to this?
I think better safe than sorry. Maybe one day in hindsight people will say they might have been overreacting For right now, it's potentially dangerous, and it's worthwhile to respond with these kinds of measures. I don't think we are panicked from where I'm sitting. I live in Madrona and they closed Madrona Elementary. I think that is the right thing to do.

Why is the virus causing more deaths in Mexico than in the U.S.?

It isn't that it's a different virus, rather the health conditions are different. Other social factors are influencing the outcome of infection, such as if people live more closely or people are malnourished.

How quickly can you develop a vaccine?
I think we'll get results pretty quickly and deeper understanding quite quickly, but what one can do about it is another matter. It takes time to interpret and collate information. It's hard to say how long it will take. Vaccines are made in eggs. For 300 million dosage, right now that's 300 million eggs. That's a huge ship you've got to turn around to do that. This virus appears to grow very slowly in eggs. That of course also impedes vaccine development.

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