# 5812
I usually try to avoid using the word `Mutant’ or `Mutation’ in my blog titles about flu because, strictly speaking . . .
All influenza viruses are the product of mutation.
Flu viruses are inherently unstable (in particularly, influenza A), and are constantly evolving and changing. Mutating. Which explains why scientists must adjust the flu vaccine nearly every year.
Of course, the media loves the word `Mutation’ – I suspect because it conjures up vivid images in the minds of their readers. And to the public, mutations are almost universally perceived as `bad’.
Earlier this week we saw a plethora of `Mutant’ headlines, including:
New bird flu virus mutation threatens Vietnam -Thanh Nien Daily
No vaccine yet for mutant bird flu ... - The Straits Times
Mutant Bird-Flu Strain Spreads in Asia - The Daily Beast
Mutant bird flu strain in Asia prompts call for scrutiny - MSNBC
While the emergence of this (relatively) new strain of H5N1 is a big story, so far we’ve seen no evidence to suggest that this `mutation’ poses any greater threat to humans than do any of the other dozen or so clades of the bird flu virus.
But that isn’t the sort of lede that sells newspapers.
Since the `M’ word seems to be on the lips of many people this week, today seems like a good day to go over how influenza viruses mutate.
Don’t worry.
I’ll keep this layman simple, mostly so I – a non-scientist - can understand it. Real scientists, however, may wish to avert their eyes.
The genetic sequence of the influenza virus can be represented by a chain of letters identifying the hundreds of amino acids that make up the viral genome.
A tiny sub-section of that chain might have an amino acid sequence that looks something like:
MKAILVVMLYTFATA
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 and repeat the process.
But being a single-strand RNA virus, the influenza virus tends to be sloppy in making copies of itself. As it replicates millions of times, tiny errors sometimes creep in. If in the process of making copies it mixes up just a single amino acid, we can end up with a mutated virus.
MKAILVVMLYTFATA
MKAILVVMLYTFATA
MKAIFVVMLYTFATA - Voila! A mutation
MKAIFVVMLYTFATA
MKAIFVVMLYTFATA
Above, I’ve swapped out the amino acid leucine (L) at position 5 for phenylalanine (F), simulating a replication error.
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 mutations in the virus are called drift, and over time the flu virus can accumulate enough changes so that last year’s vaccine is no longer effective.
And that is essentially the story behind this new 2.3.2.1 clade of the H5N1 virus. Enough antigenic changes have accumulated in its genome to allow it to evade the poultry vaccines currently in use.
Of course, mutations like these are also capable of bringing about other changes, including antiviral resistance, or perhaps increasing the virulence or transmissibility of the virus.
So while not necessarily alarming, this week’s bird flu news is certainly worthy of our attention.
Bigger changes in the influenza virus generally come about through a process known as reassortment or shift.
Reassorted viruses can result when two different flu strains inhabit the same host (human or otherwise) at the same time. Under the right conditions, they can swap one or more gene segments and produce a hybrid virus.
While far less common than drift, shift can produce dramatic changes in how a virus behaves, and has been responsible for the creation of pandemic viruses in the past.
Again this week, we’ve received news of a pair of `reassortant’ swine H3N2 flu viruses detected in children from two different states (see MMWR: Swine-Origin Influenza A (H3N2) Virus Infection in Two Children).
For those of us who were covering the earliest reports of a novel swine flu outbreak in April of 2009, this week’s report admittedly has a tinge of deja flu.
But it is important to remember that over the past 5 years (excluding the 2009 H1N1 virus) nearly 2 dozen similar novel swine flu viruses have been detected across the country. It is also probable that a number of other novel infections have escaped notice – yet so far none has been shown to spread efficiently from human-to-human.
That could change, of course - as each reassortant is a new roll of the genetic dice - and so the CDC quite understandably is encouraging enhanced local flu surveillance, and would mount a vigorous response if more cases were to start to appear.
Flu viruses have been quietly mutating and reassorting for thousands of years, but only rarely does that result in a pandemic strain. The vast majority of these mutations end up in evolution’s dustbin.
Even though we don’t always know what they signify, today we have the surveillance tools that enable us to watch some of these genetic changes when they start to appear.
And while that means we are likely to hear about a lot of potential viral threats that never materialize, it also means we may get some invaluable advance warning about the next pandemic virus before it strikes.
