# 3782
Sometimes the influenza virus is real a mystery.
Scientists have been watching intently for months to detect any mutation in the H1N1 `swine’ flu virus that might add greater virulence, or perhaps antiviral resistance, to its repertoire.
While there are many possible mutations that can occur, the truth is we don’t know what a lot of those would mean for the `fitness’ of the virus.
One of the mutations scientists thought they understood reasonably well is the (E627K) substitution in the (PB2) protein; The swapping out of the amino acid Glutamic acid (E) at position 627 for Lysine (K).
Glutamic acid (E) at this position is a hallmark of avian influenza viruses, and is believed to make the virus better adapted to replicate at the higher temperatures commonly found in birds (41C).
Human flu viruses normally have Lysine (K) at position 627. That mutation supposedly makes the virus better adapted to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract.
The H1N1 swine flu, which is a reassortment of human, swine, and avian viruses, carries this `avian’ style E627 marker.
Therefore, any change at that position from E to K (Glutamic Acid to Lysine) would be expected to improve human adaptability and potentially increase virulence and/or transmissibility of the virus.
Earlier this year we heard of an E627K mutation of the H1N1 swine flu virus detected in Shanghai (A/Shanghai/71T/2009, May 31st), which raised some eyebrows, but we’ve heard little else since then. The ProMed Mail report below doesn’t reference the Shanghai sample.
Now we get word of two virus samples from the Netherlands where this mutation has once again been observed.
But the good news, for now, is that ferret testing has shown no obvious increases in virulence or transmissibility. This comes as a genuine surprise to researchers, one of whom admits `he would have bet his car’ on this mutation increasing virulence.
This first report from The Canadian Press.
Dutch researchers find mutation linked to virulence in swine flu virus
(CP)
TORONTO — Dutch scientists are reporting they have found a key mutation in several swine flu viruses from the Netherlands, a mutation that in other flu viruses increases virulence.
But they say the mutation, on the PB2 gene, doesn't appear to cause more severe disease with the novel H1N1 virus.
The two people from whom the mutated viruses were isolated had standard cases of swine flu and when the mutated virus was tested in ferrets it didn't produce more severe disease.
ProMed Mail carried an alert on this story last night, some of which is excerpted below:
INFLUENZA PANDEMIC (H1N1) 2009 (58): THE NETHERLANDS, PB2 MUTATION
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A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Mon 28 Sep 2009
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.
<SNIP>
PB2 627K is consistently found in human influenza A viruses, but rarely in avian-derived viruses. The E627K mutation may result in enhanced virus replication efficiency in humans, possibly by adjustment to host body temperature or cellular cofactors, and has previously been shown to be associated with fatal cases of HPAI H5N1 and H7N7 virus infection in humans.
Until now, A(H1N1)v viruses with Influenza pandemic (H1N1) 2009 (57): in PB2 have not been reported, and the clinical and epidemiological relevance of our finding remains unclear.
Preliminary experiments in ferrets using reverse genetics-derived new influenza A(H1N1)v viruses with the E267K mutation in PB2 did not indicate increased shedding, virulence or transmissibility. Further experiments as well as increased molecular surveillance to monitor the situation are ongoing.
As I said at the start of this, sometimes the influenza virus is a real mystery. We’ve watched and waited for this particular amino acid substitution with the expectation that it would herald a more human adapted virus.
Now that it has appeared, and no such behavioral changes have been observed, it suggests that there may be other factors – which we don’t understand – that must occur possibly in concert with this change to make the virus more virulent.
And so the mystery deepens.
