Influenza: Our Incompetent Enemy

It’s not easy to push the explosive terror of norovirus out of the public square. It takes another virus that’s even more worrying and even more adept at spreading suffering around the world.

I speak, of course, of influenza.

This winter’s influenza season came early to the Northern Hemisphere and made a splashy debut. By the end of last week, the Centers for Disease Control reported widespread flu in 47 out of 50 states in the U.S. Some stocks of vaccines were running out. Some parts of the U.S. show signs of having hit their peak, but other places, like California, haven’t yet really experienced the full wallop of flu season. So we could be looking at several more weeks of serious trouble. Europe, meanwhile, is seeing high levels of flu infections, too. (I spoke today about the flu on KPCC–listen here.)

What makes all this all the more nerve-wracking is that influenza isn’t even bringing its A game right now. We’re not dealing with a new, super-virulent strain of influenza akin to the 1918 “Spanish flu,” which killed 50 million people worldwide. This is just regular seasonal flu–a stew of old-timer flu strains that slosh out of the tropics, heading north and south as conditions permit, and killing roughly half a million people every year. The fact that this year’s seasonal flu has overwhelmed us (shutting down some hospitals, in fact) doesn’t bode well for the inevitable moment some time in the future when we do come face to face with a much meaner flu strain.

The trouble lies not just in our creaky hospital system, but in the weapons we have on hand. There’s a flu vaccine, thank goodness, but it’s only about 62% effective. Making matters worse, well under half of Americans get vaccinated each year. If you get sick, doctors don’t have a lot of options for treatments. There are a couple antiviral drugs the CDC suggests to doctors, but it’s not clear how much (if anything) they do to alleviate symptoms. Making matters worse, the viruses are evolving resistance to those drugs. There are more anti-flu drugs in the pipeline, fortunately, but we’ll have to wait to see just how effective they are, and whether they will be wiped out by resistance as well. In October I wrote in the New York Times about new advances towards a universal flu vaccine that might provide a lifetime’s protection. While the research is heartening, it won’t help us for the next few years–if not the next few decades.

In the face of all these sobering facts, it’s easy to fall under the virus’s spell and be filled with awe. After all, with a dozen or so genes, it manages to replicate itself by the trillions and circle the globe in weeks.

But here’s the funny thing about influenza. It’s pathetic.

A team of scientists led by Jonathan Yewdell at the National Institute of Allergic and Infectious Diseases recently asked a simple question: what are the odds that an influenza virus is in good working order?

In order to infect a cell, flu viruses need to produce a protein called hemagglutinin, which forms knobs on the virus’s surface and latches onto host cells. Once the virus gets inside the cell, other proteins shut down the host cell’s natural antiviral defenses, help guide the cell to make new genes, and then help package them up. Another protein on the shell of flu viruses, called neuraminidase, opens up the host cell to allow the viruses to escape.

Yewdell and his colleagues infected cells with flu viruses and then surveyed them for these essential proteins. Time and again, they found viruses that lacked at least one of them. They tested out these defective viruses and found they failed to work as a virus should. As they report in an upcoming paper in the Journal of Virology, almost ninety percent are incapable of replicating because they’re missing at least one essential protein.

This is not some general feature of all viruses. Yewdell and his colleagues ran a similar experiment with another species, called vesicular stomatitis virus. It almost always managed to do the bare minimum and produce new viruses with all its essential proteins. Influenza stands out in its incompetence.

Yewdell and his colleagues offer up a few possible explanations for this incompetence.

–Influenza viruses mutate like mad. Mutations may be so common and so devastating that the vast majority of viruses end up unable to make at least one essential protein.

–It’s also possible that when a virus invades a host cell, it fails to get the cell to make all the essential proteins that new viruses will need.  Nobody knows the success rate for this step of influenza infection is.

–Another possible source of failure has to do with the way genes are arranged in the flu virus. Rather than being one continuous string of genetic material, the flu virus genome is broken up into eight segments. A new virus needs to swallow up a copy of all eight segments in order to have the genes for all its essential proteins. Flu viruses may be sloppy in assembling their genes.

It’s possible that all three causes are in play, or that influenza’s incompetence has yet another source. Whatever the reason, the simple fact remains: nine out of ten flu viruses are fundamental failures. Which raises the question of why there’s any flu at all.

Flu still manages to be a major threat to public health because viruses can handle failure very well. If only ten percent of viruses have all their essential proteins, they can carry on the flu virus legacy by replicating exponentially. And it may well be that the incompetent flu viruses can replicate as well. Two or more flu viruses sometimes infect the same cell at once. They may be able to help each other out, making up for the defects in their fellow viruses with their own working proteins. If one virus can’t protect itself against a cell’s defenses, another can. If one virus doesn’t have the proteins it needs to escape the host cell, another virus may open the door.

It’s almost sweet to imagine flu viruses helping each other overcome their collective weaknesses. Until, of course, that spirit of cooperation lands you in bed with a fever and the sort of aches you expect from a boxing match.

(For more information on flu and other viruses, see my book A Planet of Viruses)

Images: Doug Jordan, CDC