Thursday, April 30, 2009

RESEARCH ON FLU VIRUS


How can one bug combine genetic material from pigs, birds and humans to become so dangerous? Think of flu viruses as promiscuous, species-jumping, disguise-wearing contestants in a reality-TV show titled "Evolution Gone Wild." Virus-fighters are scrambling to keep pace, using analytical techniques that work more quickly than ever.

This show is no comedy, as illustrated by today's news about the first U.S. death in the swine-flu epidemic and the escalation of the World Health Organization's pandemic alert status. But knowing how the virus game is played could help you understand issues ranging from the difference between vaccines and antivirals to the reasons why you can't get the flu from a pork chop.

Viruses are outfitted to pry their way into your cells, hijack the protein-making machinery inside, then break their way out and proliferate. The key package is the set of RNA molecules lurking inside the virus' shell. Those single-helix RNA molecules contain the instructions for assembling a cell's proteins into more viruses.

Flu viruses are so hard to get a handle on because they can swap bits of RNA inside the cell, creating a fresh genetic patchwork that emerges as a new virus strain. The fact that the flu virus depends on RNA rather than DNA increases the likelihood of mutation, because the RNA doesn't even try to correct the errors that crop up during replication. It just lets the evolutionary chips fall where they may.

Your immune system can create antibodies that lock onto a virus and keep it from breaking into your cells. But the antibodies won't immediately come to the rescue if the virus has disguised itself through genetic recombination.

That's where vaccines enter the picture: They can sensitize your immune system to recognize the virus in a new disguise. The first step in making a vaccine is to see through that disguise. And fortunately, the quickening pace of genetic analysis is streamlining that part of the process, making it possible to track down a flu virus' identity in hours rather than days or weeks.

The rapid response paid off when it came to identifying the virus behind this month's flu outbreak. "The first specimens took roughly six hours from when the box was opened," David Daigle, a spokesman for the federal Centers for Disease Control and Prevention, told me via e-mail today.

The CDC's lab had its sequencers primed and ready to go in advance - first to identify the virus as a swine-flu strain, then to get a complete genetic sequence. "Looking at that genetic sequencing data, you can draw conclusions about the origins of this virus," said John Treanor, a virus expert at the University of Rochester.

The virus was classified as an H1N1 type - the same general type that was seen during the 1976 swine-flu outbreak, but with some novel twists. CDC official Nancy Cox said the virus' RNA mixed together bits from North American avian flu and swine flu, at least one bit from human flu, and at least two bits from Asian and European swine flu.

How did all those bits get mixed together? Pigs are regarded as particularly good "mixing vessels" for RNA swaps, because they can contract flu viruses from humans and birds as well as other swine. All those bits of RNA can recombine within the pigs' cells, resulting in lots of possible disguises for the resulting viruses. One of those genetic disguises was so successful that the virus made another species-crossing jump from pigs to humans.

Now that the virus' genetic sequence has been decoded, it can be used as a fingerprint to track its spread. "For the first time in history, we can track the evolution of a pandemic in real time," WHO Director-General Margaret Chan said at a news conference today.

Just as a refresher, here are some other scientific flu facts:
Flu infections are a fact of life for pigs, but swine flu is rarely passed along directly to humans: It takes just the right genetic twist for the virus to make the jump between species. Swine-flu virus is not passed through food. "Eating properly handled and cooked pork and pork products is safe. Cooking pork to an internal temperature of 160 degrees F kills the swine flu virus as it does other bacteria and viruses," the CDC says in its swine-flu briefing. The concern about swine-to-human transmission has more to do with being in contact with live pigs.

Vaccines train your immune system to block the molecular machinery that viruses use to break their way into your cells (a.k.a. hemagglutinin, the "H" in H1N1). Those vaccines are not designed to stop an infection once it's started. In contrast, antiviral drugs target the machinery that viruses use to break out of your cells (a.k.a. neuraminidase, the "N" in H1N1). Those drugs stop the virus' life cycle in its tracks. The current manifestation of swine flu can be stopped by the antivirals Tamiflu and Relenza (but not by amantadine or rimantadine).

As a flu virus spreads, the chances of further mutation become greater, experts say. And that means there's a chance that a deadlier virus could emerge. That's why it's particularly important to limit the spread of this latest swine-flu virus. But viruses aren't all bad: In fact, evolutionary biologists have seen signs that viruses can give some species new genetic capabilities - and viruses have been used intentionally to help humans.

Finally, here's a list of resources that delve into the science of flu viruses - including some great visualizations showing how the viruses do their thing:
Antigenic shift and antigenic drift explained 
Associated Press: Swine flu interactive 
Washington Post: Flu's severity studied 
Ars Technica: An influenza biology primer 
Swine flu updates from ScienceInsider 
Viral video from Dana-Farber Cancer Institute 


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