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Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

pjie2 said:
Hmmm. Is it a recombinant? If it's a recombinant, what did it recombine with in order to acquire H274Y? If there aren't any flanking polymorphisms that are derived from a different strain, how can you tell the difference between recombination and de novo mutation?
Click to expand...
Here is a description from last year (BEFORE pandemic H1N1 emerged)


The ability of H274Y to jump from clade to clade, as well as multiple sub-clades in 2B, as well as the rapid evolution of the 2B sub-clades, raises concerns of another vaccine mismatch, as well as the associated increase in H274Y in the H1N1 gene pool. Moreover, the match between H5N1 and the recent H1N1 isolate from Indiana raises concerns that oseltamivir resistance would develop quickly after H5N1 transmission efficiencies in humans increase, regardless of oseltamivir usage.

The rapid spread of H274Y in seasonal flu and the recent reports of increases to 100% continue to be cause for concern in seasonal and pandemic flu evolution and spread.

<a rel="nofollow" href="http://www.recombinomics.com/News/09030801/H274Y_Spread.html">Commentary</a>

.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

English Teacher said:
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Click to expand...
Since this is just a pseudo news thread because the media hasn't figured out that the sequences have been released, and the "experts" really don't want to talk about the sequences because this is no reassortment involving human H1N1 with H274Y and no Tamiflu to select H274Y, I think a discussion can carry this thread forward.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

English Teacher said:
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Click to expand...

You are correct. This IS very important (and will NOT be explained in the media or by the "experts" who were "puzzled" by the H274Y in seasonal flu, and there were no lessons learned, because they are spouting the same nonsense about "random mutations" and reassortment to explain H274Y in H1N1 pandemic flu, neither of which explains the Hong Kong sequence or circumstances.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
There is no evidence that the recombination happened in San Francisco. Pandemic H1N1 with H274Y is FIT and circulating below the radar (in MILD cases).
Click to expand...
Sorry to be lazy and pick your brains but I have not looked at the HA sequences. You say the H1N1(2009) is FIT and there are HA changes. What are you basing your fitness on? Is one of the change A193T?
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

English Teacher said:
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Click to expand...
Briefly, H274Y in H1N1 seasonal flu could not be explained by the two pillars of influenza genetics, drift by random mutation introduced by copy errors, and shifts by reassortment.

The H274Y jumped from genetic background to genetic background, eliminating reassortment, but "random errors" made no sense because there was no involvement of Tamiflu, and Tamiflu causes other resisatnce changes in H1N1 and H3N2, but all resistance was linked H274Y in H1N1. Moreover, the emergence of H274Y in the Brisbane strain (clade 2B) was linked to additional acquistions, and the key acquistions were in clade 2C (Hong Kong strain) which was co-circulating.

The acquistions in seasonal flu were detailed here

http://precedings.nature.com/documents/2832/version/1

and were due to genetic hitchhiking and recombination - and the gateway from H274Y in H5N1 and H274Y in H1N1 was the Indiana seasonal flu sequence, which was the same gateway used to move H274Y from seasonal H1N1 to pandemic (swine) H1N1.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

JJackson said:
Sorry to be lazy and pick your brains but I have not looked at the HA sequences. You say the H1N1(2009) is FIT and there are HA changes. What are you basing your fitness on? Is one of the change A193T?
Click to expand...
Fitness is based on infection of Hong Kong teenage who was not taking Tamiflu.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

I have to break for tonight, and have morning meetings, so I won't be participating much until tomorrow afternoon (but not for lack of interest).
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

English Teacher said:
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Click to expand...

We can definitely discuss the science on this thread. Thanks for asking English Teacher.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

English Teacher said:
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Click to expand...
The real gateway between H274Y on H1N1 seasonal flu and moving it to H1N1 pandmeic flu is the sequence seen in Indiana last year. It had the key change that allowed H274Y to go from H5N1 to H1N1, and that same change allows for H274Y to go from seasonal H1N1 to pandemic H1N1.

Pandemic H1N1 can also get H274Y from H5N1 and some of the new polymorphisms on H1N1 link back to H5N1, which is why pandmeic H1N1 in countries like Egypt, Indonesia, Vietnam, and India may be major problems.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

English Teacher said:
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Click to expand...

Here is the key travel log for H274Y

gb|GQ351316.1| Influenza A virus (A/Hong Kong/2369/2009(H1N1)... 36.2 0.73
gb|EU567011.1| Influenza A virus (A/Indiana/01/2008(H1N1)) se... 36.2 0.73
gb|DQ493078.1| Influenza A virus (A/Vietnam/CL2009/2005(H5N1)... 36.2 0.73
gb|DQ250165.1| Influenza A virus (A/Vietnam/CL2009/2005(H5N1)... 36.2 0.73
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
Pandemic H1N1 can also get H274Y from H5N1 and some of the new polymorphisms on H1N1 link back to H5N1, which is why pandmeic H1N1 in countries like Egypt, Indonesia, Vietnam, and India may be major problems.
Click to expand...


Can you elaborate on this ? None of these sequences are from geographic areas where H5N1 is in humans (recently) so I do not understand your comment.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

For those interested in the historic nature of the Hong Kong sequence, this is the NBCI pandemic H1N1 front page yesterday afternoon:

July 06, 2009, 8 submitted by Beijing Institute of Microbiology and Epidemiology, China; 8 by University of Padova, Italy; 3 by Centre for Health Protection, Hong Kong; 2 by University of Florence, Italy; 8 by WRAIR:
<TABLE border=0 cellPadding=2><THEAD><TR><TD></TD><TH>PB2</TH><TH>PB1</TH><TH>PA</TH><TH>HA</TH><TH>NP</TH><TH>NA</TH><TH>MP</TH><TH>NS</TH></TR></THEAD><TBODY><TR vAlign=top><TH align=left>Influenza A virus
(A/Beijing/502/2009(H1N1))
</TH><TD>GQ290112</TD><TD>GQ290111</TD><TD>GQ290105</TD><TD>GQ290106</TD><TD>GQ290109</TD><TD>GQ290107</TD><TD>GQ290108</TD><TD>GQ290110</TD></TR><TR vAlign=top><TH align=left>Influenza A virus
(A/Firenze/10/2009(H1N1))
</TH><TD></TD><TD></TD><TD></TD><TD>GQ351319</TD><TD></TD><TD>GQ351320</TD><TD></TD><TD></TD></TR><TR vAlign=top><TH align=left>Influenza A virus
(A/Hong Kong/2369/2009(H1N1))
</TH><TD></TD><TD></TD><TD></TD><TD>GQ351314</TD><TD></TD><TD>GQ351316*</TD><TD>GQ351315</TD><TD></TD></TR><TR vAlign=top><TH align=left>Influenza A virus
(A/Italy/85/2009(H1N1))
</TH><TD>GQ351287</TD><TD>GQ351288</TD><TD>GQ351289</TD><TD>GQ351290</TD><TD>GQ351291</TD><TD>GQ351292</TD><TD>GQ351293</TD><TD>GQ351294</TD></TR><TR vAlign=top><TH align=left>Influenza A virus
(A/Santo Domingo/572N/2009(H1N1))
</TH><TD>CY041957</TD><TD>CY041958</TD><TD>CY041959</TD><TD>CY041960</TD><TD>CY041961</TD><TD>CY041962</TD><TD>CY041963</TD><TD>CY041964</TD></TR><TBODY></TBODY></TABLE>* This sequence has the H274Y mutation that might confer resistance to Oseltamivir.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Kudos to the Health Protection Agency in Hong Kong for the prompt release of the NA sequence with H274Y.

It is of note that neither Denmark nor Japan have released the sequences (apologies from Japan on withholding data for publication notwithstanding).

Journalists should hold their feet to the fire and ask WHY are the NA sequences with H274Y NOT public.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Toaster2 said:
Can you elaborate on this ? None of these sequences are from geographic areas where H5N1 is in humans (recently) so I do not understand your comment.
Click to expand...
All of the sequences in the travel log have H274Y and downstream matches (and all are from humans, including the two H5N1 sequences from Vietnam).
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

When I looked up the 3 different NAs, I found an "F" for Indiana, while there is a "Y" for Vietnam and HK. What's the "F"?

ABB76122 A/Vietnam/CL2009/2005(H5N1)
ACB11804 A/Indiana/01/2008(H1N1)
ACT10319 A/Hong Kong/2369/2009(H1N1)
Click to expand...

If I'm reading it right, concensus is the top line below, then the 3 above:

YYY
. . .
F . .
. . .

(added: starting in position 274)

.
 
Last edited:
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

AlaskaDenise said:
When I looked up the 3 different NAs, I found an "F" for Indiana, while there is a "Y" for Vietnam and HK. What's the "F"?



If I'm reading it right, concensus is the top line below, then the 3 above:

YYY
. . .
F . .
. . .

(added: starting in position 274)

.
Click to expand...
F is phenylalanine, is upstream, and is in H1 seasonal flu.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
The real gateway between H274Y on H1N1 seasonal flu and moving it to H1N1 pandmeic flu is the sequence seen in Indiana last year. It had the key change that allowed H274Y to go from H5N1 to H1N1, and that same change allows for H274Y to go from seasonal H1N1 to pandemic H1N1...........
Click to expand...

I understood the above statement to mean that Indiana/01/2008 had 274Y, which is why I was surprised to see an "F". I'm still not understanding how the "F" can create a "Y", but then I'm not a sequences-guru.

.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

AlaskaDenise said:
I understood the above statement to mean that Indiana/01/2008 had 274Y, which is why I was surprised to see an "F". I'm still not understanding how the "F" can create a "Y", but then I'm not a sequences-guru.

.
Click to expand...
F is at position 273. Tamiflu resistance is at position 274 (where all have Y as in H274Y).
For H1 seasonal flu sensitive is FHY, resistant is FYY.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

<a rel="nofollow" href="http://www.recombinomics.com/News/07070901/H274Y_HK_Seq.html">Commentary</a>
 
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