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**logicalAmerican** · May 4, 2009, 04:53 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Anything in NS? Didn't Dr Niman say that he was going to take a look? See http://www.flutrackers.com/forum/sho...d.php?t=100274. Did he ever get back?

**AlaskaDenise** · May 4, 2009, 05:08 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Originally posted by logicalAmerican View Post

Anything in NS? Didn't Dr Niman say that he was going to take a look? See http://www.flutrackers.com/forum/sho...d.php?t=100274. Did he ever get back?

Mamabird said the NS1/92 gene (the viral bullet-proof vest so it won't be killed by most of the human-immune-system ammunition) was okay! It's not in the other widely-circulating influenza/A.....so I left it out of this thread.

I believe that has only existed in (edited: 1918/H1N1=error) and current HP (high path) H5N1.

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**logicalAmerican** · May 4, 2009, 06:35 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Is PB1 F2 N66S even in the running? Or disqualified as belonging strictly to H5N1?

See http://www.flutrackers.com/forum/showthread.php?t=37360

**AlaskaDenise** · May 4, 2009, 06:57 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Since it is not in a widely circulated human influenza, I'd say the probability is lower than the others.

My purpose for this thread is to explore the more likely combinations that we may be dealing with in the next 6-12-18 months, rather than less likely worse case scenerios. I fear the current events may foster complacency and if we understand the likely future of this virus, we can maintain a realistic view of the situation.

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**AlaskaDenise** · May 4, 2009, 09:59 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

We should also consider the opposite - what would be the result of A/H3N2 or seasonal A/H1N1 acquiring genes from swine A/H1N1?

Which H1N1 will come out the stronger? Old, new, which combination, or will we have 2 somewhat different circulating A/H1N1?

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**AlaskaDenise** · May 5, 2009, 05:12 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

IOH has alerted us to the possibilty of a mixture with H9N2, a fairly-well humanized flu circulating in birds, with occasional human infections.

What pathogencity factors that will bring to the mix I'm not sure at this point.

His link:

Minimal molecular constraints for respiratory droplet transmission of an avian?human H9N2 influenza A virushttp://www.pnas.org/content/106/18/7565.short?rss=1

Thanks IOH.

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**Mamabird** · May 5, 2009, 06:07 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Provided in 1, below are the problem amino acids associated with the currently circulating Swine Flu. These are generally found in every pandemic virus and most seasonal flu viruses, and some relate to sensitivity to antivirals, etc. All the available Swine Flu virus gene sequences have these human/problem characteristics.

1. PB2: A199S; PB1 N(T)375S; PB1-F2 P(R)48Q; PA T129I and S409N; HA E190D, S221P, F251L and Y258F; NP V33I, R100V and Q357K; MP K27R, I168T and N224S; M2 none; NS2 F55L; NA none.

Provided in 2, below are those amino acids that this bug has not yet obtained, but if obtained, could be problematic. Some are more important that others. None of the Swine Flu viruses have these characteristics as far as I know, but we should all keep an eye out for them>

2. PB2 L(F)475M, D567N and E627K; PB1 none; PB1-F2 P28L, D55N, I(V)100A and T552S; HA multi-basic amino acids at the clevage site (usually associated only with poultry infections); NP G16D, L283P and F313Y; MP I15V, K101R, A166V and N207S; M2 E16G and S20N; NS none; NS2 none; NA H274Y and N294S.

In other words, the Swine Flu virus has about half of the problem amino acids already in its tool box. The only other viruses even close to this are some H9N2 viruses circulating widely in Hong Kong and H7N7 in the Netherlands. As to the wild type avian viruses, only the North American variety come close.

Take away: This is a problem virus that bears watching closely. Reassortment with seasonal flu or H5N1 could be interesting.

**AlaskaDenise** · May 5, 2009, 06:27 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

This is a problem virus that bears watching closely

Thankfully, you're hard at work doing just that.

That's a lot of variables to look for. It would seem that given all the possiblities and several viruses to pick from, the new H1N1 (swine) cannot avoid picking a few morsels from the menu.

The importance of sharing sequences between all countries is now quite obvious to the public (and MSM).

Thanks Mamabird for sharing your expertise.

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**Treyfish** · May 5, 2009, 06:39 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

INFLUENZA A (H1N1) - WORLDWIDE (11): COINCIDENT H3N2 VARIATION

Date: Tue 5 May 2009 12:08:07 -0700
From: Danuta Skowronski
<Danuta.Skowronski@bccdc.ca>

Recent mutations away from the 2008-09 influenza vaccine strain among
North American A/H3N2 virus coincident with emergence of novel A/H1N1
--------------------------------------------------------------------------------------------
The BC [British Columbia] Centre for Disease Control (BCCDC) Virology
Laboratory routinely sequences the hemagglutinin (HA) gene from a
sample of influenza viruses submitted each season by community
clinicians, hospitals and care facilities across the province of
British Columbia, Canada.

Until mid-February 2009, amino acid sequences of the HA gene of H3
viruses in BC were virtually identical to the vaccine strain [A/
Brisbane/10/07 (H3N2)], with the exception of a Lys189Gln change at
antigenic site B. In early March 2009, however, we detected
additional differences from the vaccine strain among BC viruses
collected from facility outbreak settings at antigenic site B to
include change from the vaccine strain at Asp160Lys (as well as
Lys189Gln) and at antigenic site D at Val229Ala. These changes were
seen only in viruses from care facility outbreaks and not from
community specimens submitted by our network of sentinel physicians.

After the novel North American influenza A/H1N1 virus was reported
from Mexico as well as California during the 4th week of April 2009,
specimens from returning travelers and others in BC with
influenza-like illness were tested including influenza subtype
determination and sequencing. Among approximately 900 respiratory
specimens submitted to the BCCDC laboratory between 24 Apr 2009 and 3
May 2009, the majority was negative for influenza; an equal number of
influenza A detections were of the H1 or H3 subtype.
We have sequenced the HA gene of one of the H3 viruses from an ill
traveler returning from Mexico and find it shares the same amino acid
changes noted above.

These amino acid substitutions do not fulfill the criteria proposed
by Cox as corresponding to meaningful antigenic drift (requiring at
least 2 amino acid substitutions at 2 or more defined antigenic sites
A-E)[1] They may, however, signal important evolution in the HA gene.
During late March and early April 2009 we reported an unexpected
number of late-season care facility outbreaks due to H3 influenza. We
should thus remain vigilant for further H3N2 evolution and reduced
vaccine relatedness since A/Brisbane/10/07(H3N2) has been retained as
the proposed vaccine component for both the 2009 southern and 2009-10
northern hemisphere influenza seasons. Ongoing gene sequence analysis
of H3 viruses from other countries would be informative. In BC, these
H3 mutations arose sometime in early March 2009 and we observe at
least one returning traveler to have likely acquired illness due to
this virus in Mexico (specimen collected in BC 26 Apr 2009). We thus
also wonder to what extent the profile of influenza-like illness
initially reported from mid-March in Mexico may in part be attributed
to this H3N2 variant in addition to emergence of the novel A/H1N1 virus.

Reference:
----------
[1] Cox NJ, Bender CA. The molecular epidemiology of influenza
viruses. S/eminars in /VIROLOGY 1995; 6:359-370.

Authors:
Danuta M Skowronski MD, MHSc, FRCPC, Tracy Chan BSc, Naveed Z Janjua
MD, DrPH, Travis Hottes MSc, Annie Mak BSc, Martin Petric PhD, FCCM,
Mel Krajden MD, FRCPC, Patrick Tang MD, PhD, FRCPC, David Patrick MD,
MHSc, FRCPC, Robert Brunham MD, FRCPC.

At: The BC Centre for Disease Control Provincial Laboratories and
Epidemiology Services

--
Communicated by:
Phil Temples
<phil@temples.com>

[The novel observations reported above reveal the occurrence of
progressive variation in the HA gene of H3N2-type seasonal influenza
virus which if maintained may have consequences for the outcome of
the next seasonal influenza vaccination programme. More intriguing is
the observation that the same novel mutational changes were detected
among viruses isolated from patients in care facilities in Canada as
in a virus isolated from a traveler from Mexico. The authors suggest
that the profile of influenza-like illness initially reported from
mid-March 2009 in Mexico may in part be attributed to this H3N2
variant in addition to the emergence of the novel A/H1N1 virus. This
is a matter that merits urgent investigation as it might help to
explain some of the unusual features of the current epidemic. - Mod.CP]

**gsgs** · May 5, 2009, 10:17 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

PB1-F2 is in most of the similar viruses
it had been responsible for 1918 virulence
PB1 was exchanged in 1957 and 1968

suppose this virus gets PB1 from seasonal flu - they should test it
(and tell us the result)

**gsgs** · May 5, 2009, 10:19 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

human,avian,swine - FluTrackers News and Information

http://www.flutrackers.com/forum/showthread.php?t=102738

**AlaskaDenise** · May 5, 2009, 11:03 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Originally posted by gsgs View Post

PB1-F2 is in most of the similar viruses
it had been responsible for 1918 virulence
PB1 was exchanged in 1957 and 1968

suppose this virus gets PB1 from seasonal flu - they should test it
(and tell us the result)

Could clarify "similar" and "exchanged" please?

To take your statements in reverse sequence ... PB1 is in seasonal flu, it is responsible for 1918 virulence , & it is in "similar" viruses - implies seasonal and "similar" viruses should have a 1918 virulence (but they don't). Maybe you could restate the logic there. All these details are terribly confusing for many people.

A link to a scientific paper for PB1-F2 A/1918 would be nice for newcomers.

Thanks.

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**gsgs** · May 5, 2009, 11:43 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

I already posted the link (N66S in PB1-F2 responsible for 1918-virulence
or such, Palese et.al AFAIR)

exchanged = reassorted
1957 : new Avian HA,NA,PB1
1968 : new Avian HA,PB1

similar = American H1N1 in swine since 1998

FluTrackers News and Information

http://www.flutrackers.com/forum/showthread.php?t=37360

seasonal flu is not so virulent, because we are adapted,partly immune to it.
Also there are other markers for virulence , we don't know how they "cooperate"

**AlaskaDenise** · May 5, 2009, 11:59 PM

Re: What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

Thanks.

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What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

What's on the genetic menu for New A/H1N1 and seasonal A/H1N1 & A/H3N2 swapping?

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