Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

[HenryN]

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

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?

Fitness is based on infection of Hong Kong teenage who was not taking Tamiflu.

[HenryN]

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.

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.

[JJackson]

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

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).

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?

[HenryN]

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.

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.

[HenryN]

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.

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.

[English Teacher]

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.

[HenryN]

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

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?

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>

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[HenryN]

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

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?

The donor sequence was described last year (before the pandemic H1N1 was known)

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

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[HenryN]

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

Did anyone in her family, or any traveling HK acquaintances, have a lingering seasonal H1N1 from HK - thereby setting the stage for a dual infection?

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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).

[HenryN]

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

Thanks. Sorry did not read closely enough just looked at the sequences. You were just giving Jersey Girl as a close pre change relative.

Identical pre-change in NA (also has one of the three HA polymorphisms).

[HenryN]

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

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?

Here is the H274Y travel log (sequences that can donate H274Y)

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

[JJackson]

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

Thanks. Sorry did not read closely enough just looked at the sequences. You were just giving Jersey Girl as a close pre change relative.

[HenryN]

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

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?

Coincidences get very old very fast. The recombination leads to exchanges of SNPs, as described in the Nature Precedings paper. The donor sequence would be seasonal H1N1, which matches on the 3' side (like A/Indiana/1/2008).

[HenryN]

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

If it is YHY rather than YYY what is conferring the resistance?

There is only one resistant sequence (from Hong Kong). The NJ sequence matches at all other positions.

[AlaskaDenise]

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

Did anyone in her family, or any traveling HK acquaintances, have a lingering seasonal H1N1 from HK - thereby setting the stage for a dual infection?

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