# 4436
The `buzz’ this morning surrounds an article out of India describing the discovery of a `mutation’ in the PB2 gene segment of the H1N1 virus that has been detected in 3 patients.
Mutations, of course, are common with influenza viruses. Most turn out to be of little importance.
On rare occasions mutations can convey a significant biological advantage to the virus.
While this article is infused with an extraordinary amount of `disease geek-speak’ for a newspaper story, we get surprisingly little hard information about this reported genetic change in the virus.
First the article, then a few comments.
H1N1 virus shows genetic mutation, 'but not a worry'
Umesh Isalkar, TNN, Mar 16, 2010, 07.32am IST
PUNE: The swine flu virus isolated from the throat swab samples of three H1N1-infected patients at the National Institute of Virology (NIV) has shown a small genetic mutation in the polymerase 2 (PB2) gene, NIV director A C Mishra told TOI on Monday.
However, Mishra said there was no cause for worry as the virus was still not resistant to oseltamivir, which is an active ingredient in Tamiflu.
It may be noted that a small genetic mutation was earlier detected in the haemagglutinin (HA) region of the virus as well while testing the throat swab samples of two patients who eventually succumbed to the H1N1 infection.
The PB2 mutation has previously been associated with increased efficiency of replication and possible virulence changes in other influenza A viruses. “However, we did not find such increased efficiency of replication or increased virulence in the isolates of the swine flu virus in which we have noticed mutation of the PB2 gene. The mutation is not very significant in that sense,” said Mishra.
Consulting microbiologist and immunologist Siddharth Dalvi said, “The PB gene makes a protein that is responsible for viral replication. Since this enzymic protein is not directly involved in the immune responses, point mutations in this gene may not be of immediate clinical impact. However, it may, in theory, change the way the virus replicates.”
Most RNA viruses (including influenza virus) replicate their genome by using the viral enzyme to make copies from the parent RNA. “This enzyme has a weak proof-reading activity, that is, checking if the right nucleotides have been incorporated in the genome. Hence, over time, point mutations are bound to happen in the genome of these viruses. In fact, we would be surprised if they don’t. The majority of these mutations may not have any significance, either for the virus, or for the host,” said Dalvi.
Left out of this reassuring virology lesson are a few key (but basic) facts that would have gone a long ways towards clarifying the significance of this story.
What mutation in the PB2 gene are they talking about? (Possibly E627K, but never actually stated)
When were these samples collected?
Were these three patients epidemiologically connected in any way?
What of the course of illness and outcome for these three patients?
I ask these questions - not because I’m particularly concerned over the impact of this particular mutation - but simply in the interest of clear and concise reporting.
Saying that they found a mutation in the PB2 gene is, quite frankly, about as precise as reporting `a flood somewhere in New England’.
Accurate as far as it goes, but not terribly helpful.
If this report sounds a little familiar, it may be because last September Dutch scientists reported that they had found a couple of patients with a PB2 mutation (E627K) that – to their surprise – conveyed no detectable biological advantage to the virus.
ProMed Mail carried an alert on this story on September 27th , some of which is excerpted below:
INFLUENZA PANDEMIC (H1N1) 2009 (58): THE NETHERLANDS, PB2 MUTATION
From: Marion Koopmans
<Marion.Koopmans@rivm.nl>We would like to report 2 patients in The Netherlands, diagnosed with influenza pandemic A(H1N1) 2009 virus infection that had a mutation (E627K) in the basic polymerase 2 (PB2) protein. This mutation has previously been associated with increased efficiency of replication and possible virulence changes in other influenza A viruses.
The investigation identified a specific geographic region in the north of The Netherlands as the place where viruses with the same genetic background have circulated between mid July and mid August [2009]. No other cases carrying the PB2 mutation have been identified.
The E627K mutation in novel H1N1 was widely expected to expedite viral replication in humans. The fact that it apparently doesn’t was of considerable surprise to scientists around the world.
We’ll have to wait for better reporting on the Indian mutation before we can know with certainty exactly what mutation they are talking about.
If it turns out to be E627K, their observations would appear to match those of the researchers out of the Netherlands last year.
Obviously, we’ll keep an eye on this story in hopes of more details.
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