Comments on: Influenza A/Mexico/2009 (H1N1): Absence of crucial virulence marker

By: It’s not easy to make the 2009 H1N1 influenza virus a killer

It’s not easy to make the 2009 H1N1 influenza virus a killer — Fri, 12 Mar 2010 13:32:30 +0000

[...] second RNA segment of some influenza virus strains encodes a protein called PB1-F2 that might contribute to virulence. Speaking about the 2009 pandemic H1N1 strain, Peter Palese noted that “If this virulence marker [...]

By: Influenza PB1-F2 protein and viral fitness

Influenza PB1-F2 protein and viral fitness — Fri, 28 Aug 2009 18:14:12 +0000

[...] The latter protein is believed to be an important determinant of influenza virus virulence. The absence of a full-length PB1-F2 protein has been suggested as one possible determinant for the low pathogenicity of the 2009 influenza H1N1 [...]

By: profvrr

profvrr — Fri, 14 Aug 2009 00:14:00 +0000

I'm not sure what you are referring to. Perhaps the R value – the
average number of secondary infections resulting from one infected
host? The R value for the 1918 virus has been estimated at 2-3. I've
seen similar numbers for the 2009 H1N1 virus.

By: profvrr

profvrr — Thu, 13 Aug 2009 17:14:00 +0000

By: John Rogans MD

John Rogans MD — Tue, 21 Jul 2009 19:10:51 +0000

One of the truly deadly features of the 1918 isolates was, I believe a replication rate of 40,000. (If that is the correct terminology. I am not a virologist.) Is there a comparable value for the 2009 virus?

JR, MD

By: profvrr

profvrr — Tue, 21 Jul 2009 16:23:32 +0000

An interesting addition to the Nature paper would have been to mutate
the 2009 H1N1 virus so that full-length PB1-F2 is produced, and then
determine the virulence of the virus in animals. It's not clear to me
that making PB1-F2 is all that would be needed to increase virulence
of the H1N1 S-OIV virus in humans.

By: John Rogans MD

John Rogans MD — Fri, 17 Jul 2009 14:08:09 +0000

The big question seems to be –

Can the current H1N1 virus mutate and somehow acquire the PB1-F2 protein and become a killer?

JR, MD

By: profvrr

profvrr — Mon, 11 May 2009 18:14:11 +0000

The two mutations you mention could occur very easily. For a 10 kb
viral RNA, there is one new mutation incorporated per new molecule
synthesized. If 10,000 viral RNA molecules are made per cell (not
unreasonable) then all genome positions could be altered. The point is
that two base changes are no obstacle to an RNA virus. The question is
whether making the F2 protein would be compatible with the replication
of this particular virus, to which we don't yet have an answer.

By: Brian Foley

Brian Foley — Thu, 07 May 2009 16:24:00 +0000

The sequence you were looking at, is not the only one to have no functional PB1-F2 reading frame. For example GQ117034 also lacks it. So it is not just a sequencing error, or one clone lacking it. I do not know how important the PB1-F2 protein is, for viral “fitness” or pathogenicity or anything.

By: giuseppe

giuseppe — Wed, 06 May 2009 22:31:00 +0000

looking at pb1-f2 gene of h1n1 2009 i see:
(nucleotide position are referred to this sample from ncbi database: FJ998226 (A/Mexico/InDRE4487/2009(H1N1)))
start codon at position 105..107 (on a different frame from pb1 gene, starting at position 11..13)
first stop codon, at position 138..140 (after 11th codon)
a second stop codon at position 276..278 (after 57th codon)
and another stop codon at position 366..368 (after 87th codon)
according to this http://findarticles.com/p/articles/mi_m0GVK/is_...
at least a 78 a.a. polypeptide is needed to have a functional pb1-f2 protein, so should be required two base mutations:
139 A=>T and 277 A=>G
so my question is: is it possible to estimate the probability that this mutations occurs?
(are there any data on influenza A mutation rate for this gene or locus?)

By: profvrr

profvrr — Tue, 05 May 2009 23:09:36 +0000

Yes, the 1918 isolates were from September-November 1918. So we cannot
answer your good question, unless earlier specimens turn up.

By: profvrr

profvrr — Mon, 04 May 2009 17:47:58 +0000

You would have to remove the first stop codon and a second as well
downstream. Then position 66 would be an asparagine, which is found in
the less virulent strains.

By: profvrr

profvrr — Mon, 04 May 2009 16:58:59 +0000

The sequences of many Mexican isolates have now been released at
GISAID – Global Initiative on Sharing Avian Influenza Data.
Registration is required to access the data. I do not understand why
the sequences were released here and not at NCBI.

I'll be looking at these sequences today with respect to the PB1-F2 question.

By: ocohen

ocohen — Mon, 04 May 2009 00:05:12 +0000

the 1918 pandemic started in springtime as a mild disease, fizzled over the summer, and started killing with a vengeance in the fall. Are there any data to suggest that the early strain lacked the PB1-F2 signature and then acquired it by mutation by the time it re-emerged in the fall? Presumably the reconstructed 1918 sequences from victims buried in permafrost are from after the fall of 1918?

By: nobody

nobody — Sun, 03 May 2009 21:38:22 +0000

Looks like an Asparagine. http://www.ncbi.nlm.nih.gov/nuccore/229299522?f...

By: nobody

nobody — Sun, 03 May 2009 21:36:21 +0000

Looks like an Asparagine. http://www.ncbi.nlm.nih.gov/nuccore/229299522?f...

By: Schweinegrippe - Ist Panik berechtigt? | homo homini lupus

Schweinegrippe - Ist Panik berechtigt? | homo homini lupus — Sun, 03 May 2009 18:19:31 +0000

[...] von Oseltamivir oder Zanamivir Lancet: Swine influenza: how much of a global threat? Virology blog: Influenza A/Mexico/2009 (H1N1): Absence of crucial virulence marker New York Times: No Signs of Sustained Global Spread of Swine Flu [...]

By: M. A. Ramakrishnan

M. A. Ramakrishnan — Sun, 03 May 2009 13:47:31 +0000

Please correct as PB1-F2 (including text)

By: Matt Dubuque

Matt Dubuque — Sun, 03 May 2009 13:21:05 +0000

Thanks, but the issue is why the profound and protracted delay in posting the entire sequences publicly for the world to see? It's urgent and important and has already been done for several US isolates.

Why the delay? There has simply been no satisfactory explanation.

By: Anonymous

Anonymous — Sun, 03 May 2009 09:15:10 +0000

There is some information about Mexican isolates here:
http://scienceblogs.com/digitalbio/2009/04/did_...

Nickel summary: those who have seen data from Mexico say the sequences are highly similar to what we have seen.

By: Matt Dubuque

Matt Dubuque — Sun, 03 May 2009 07:37:32 +0000

How do we know this analysis applies to what has been afflicting the Mexican population?

There has been no release of any Mexican sequences, as far as I know.

Therefore, scientifically speaking, how is this different from anecdotal evidence?

I'm not trying to be harsh, but isn't this speculative without this Mexican sequences from a purely objective, rational, scientific view?

By: dave

dave — Sat, 02 May 2009 22:25:32 +0000

And if a single point mutation removes the stop codon, what do you see at position 66 and how do you think virulence will be affected?

By: profvrr

profvrr — Sat, 02 May 2009 19:54:11 +0000

Excellent point…a single point mutation would remove the stop codon,
and produce a PB2-F2 protein. You can see from the sequence that's all
it would take. Of course, reassortment could also do it, but it's not
necessary.

By: Chris Upton

Chris Upton — Sat, 02 May 2009 19:45:17 +0000

But what is needed to create a functional PB2-F2 gene?
Single point mutation or new re-assorted virus?