# 3926
Several times over the past few months we’ve seen press accounts that suggest that the novel H1N1 `swine’ flu has `mutated’ into a more virulent strain.
While some minor variations have been detected, so far, we’ve not seen any scientific evidence of any `serious’ mutations in the virus.
Despite these newspaper accounts.
`Serious’ meaning changes that would make the vaccine less effective, or that would render antivirals ineffective, or increase the transmissibility or virulence of the virus.
There have been a few dozen reports of Tamiflu resistant viruses, but little to suggest that they are spreading widely at this time.
Could it happen? Sure.
And some scientists are surprised we haven’t seen more variation in the virus than we have to date. Based on the (admittedly limited) genetic sequencing that’s been done around the world, the virus appears to remain remarkably stable.
First, an excellent background story on one of the labs in the United States, at the University of California San Francisco, that is doing "deep sequencing” of swine flu virus samples, looking for dangerous mutations.
Then we’ll talk a bit about how mutations occur. Go ahead and read the whole thing. I’ll wait.
UCSF scientists track swine flu virus for tiny changes that would cause big problems
By Lisa M. Krieger
Posted: 10/31/2009 08:55:00 PM PDT
SAN FRANCISCO — As the H1N1 flu virus spreads at breakneck speed, a team of local scientists are close behind. They are watching its evolution through a cutting-edge technology in hopes of answering the question: Where did it come from — and where is it going?
Their lab at the University of California-San Francisco holds a growing international collection of viral samples, including some from San Jose swabbed from the noses of sick people, since the first days of the swine flu epidemic. Genetic analysis of each sample will alert researchers to any tiny change that would create a giant problem.
So far, the swine flu virus seems to be evolving slowly. But a small mutation could create resistance to drugs.
The scientific sleuths are most worried about a big genetic leap — such as in 1918, when a mild virus turned deadly, killing 20 million to 40 million people. If such a leap does happen, the lab hopes to detect it early, triggering more aggressive treatment, quarantining and prevention measures.
Viruses, and particularly influenza viruses, are infamous for their ability to mutate or change in relatively short periods of time. Of course, it isn’t enough for a mutation to occur.
The mutated virus must also be `biologically fit’ enough to replicate (preferably as - or more - efficiently than it's predecessor), and able to transmit efficiently to other hosts.
Otherwise, it becomes an evolutionary dead-end.
The two most common ways for a flu virus to mutate are by making `replication errors’ in it’s genetic sequence, or by combining or reassorting with another virus.
A little science. Don’t worry, I’ll try keep to this at the junior high school level, as that’s about all I am capable of.
Real scientists, for their own sanity, should avert their eyes from this intentionally simplified explanation.
Let’s look first at how a replication error might occur.
The genetic sequence of the flu virus can be represented by the letters of the amino acids that make up the viral genome. These are long chains comprised of hundreds of amino acid molecules.
A tiny sub-section of that chain might have a sequence something like:
NPECESLSTASSWSYI
As the virus inhabits a cell, and begins to replicate, it makes thousands of copies of itself which then burst out of the cell after a few hours and go on to infect other cells.
Those cells, in turn, make copies that go forth to infect more cells.
But being a single-strand RNA virus, the influenza virus tends to be sloppy in making copies of itself. Errors sometimes creep in. If in the process of replicating it mixes up just a single amino acid, we can end up with a mutated virus.
NPECESLSTASSWSYI
NPECKSLSTASSWSYI < – A mutation!
NPECKSLSTASSWSYI
NPECKSLSTASSWSYI
NPECKSLSTASSWSYI
Above, I’ve swapped out the amino acid Glutamic acid (E) at position 5 for Lysine (K). Assuming the result is a `biologically fit’ and competitive virus (most aren’t), then it may go on to infect other cells, and conceivably, other hosts.
Of course, that doesn’t mean it will make the virus more dangerous. A mutation can make the virus less virulent or less transmissible. Or it may simply have no effect at all.
These small changes in the virus are called antigenic drift, and over time changes in the virus can accumulate to the point that last year’s vaccine is no longer effective. They can also bring about antiviral resistance, or even increase the virulence or transmissibility of the virus.
Big jumps, or mutations in the virus generally come about through a process called reassortment. And that happens when two different flu strains inhabit the same host (human or otherwise) at the same time.
That isn’t as rare as you might think.
In a study entitled:
Aetiology of influenza-like illness in adults includes parainfluenzavirus type 4
J Med Microbiol 58 (2009), 408-413; DOI: 10.1099/jmm.0.006098-0
. . . more than 10% of those tested had two or more concurrent viral (but not necessarily influenza) infections.
It is possible for two compatible flu viruses to swap genetic material and produce a hybrid virus. This is called reassortment, or antigenic shift. The result can be a new – or novel – virus to which humans have little or no immunity.
This is how pandemics occur.
Once again, most reassortments and mutations are evolutionary dead-ends. But every once in great while, we get a new, `fit’ virus that takes off. Which is exactly how the current H1N1 swine flu virus came to be.
It is the end result of multiple reassortments of swine, human, and avian viruses in pigs over the years.
While the odds of a mutation or a reassortment occurring in any one person (or animal host) is extremely low, when you spread a virus across millions (or tens of millions) of hosts, you increase the odds dramatically.
Which is why scientists are watching so carefully for any change to the virus.
But the first indication of a change may not come from a laboratory. It will probably come from an observed change in the way the virus behaves, or presents in patients; a change in patient age profiles, a change in severity or mortality, or a resistance to antivirals.
So we keep an eye on reports, like the ones we are seeing out of the Ukraine and India this week, for hints that something may be changing with this virus.
So far, we’ve been lucky. Similar reports in Argentina and Mexico have not led to the discovery of a more virulent strain.
Hopefully our luck continues to hold.
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