Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

[HenryN]

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

gb|GQ365446.1| Influenza A virus (A/Sapporo/1/2009(H1N1)) seg... 36.2 0.73
dbj|AB434384.1| Influenza A virus (A/swine/Kyoto/3/1979(H1N1)... 36.2 0.73
gb|CY028179.1| Influenza A virus (A/swine/Tennessee/3/1978(H1... 36.2 0.73
gb|CY027291.1| Influenza A virus (A/swine/Ohio/23/1935(H1N1))... 36.2 0.73
gb|EU139823.1| Influenza A virus (A/swine/Iowa/15/1930(H1N1))... 36.2 0.73
gb|CY009628.1| Influenza A virus (A/swine/1931(H1N1)) segment...
gb|AF091308.1|AF091308 Influenza A virus (A/swine/Iowa/15/30 ... 36.2 0.73
gb|U11703.1|IAU11703 Influenza A virus (A/swine/St-Hyacinthe/... 36.2 0.73

[HenryN]

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

It is worth noting that 1918 was a recombinant between human A/WSN/33 and swine A/swine/Iowa/15/1930.

[wotan]

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

It is worth noting that 1918 was a recombinant between human A/WSN/33 and swine A/swine/Iowa/15/1930.

Maybe I'm being dense, but I am lost here. Unless I am reading it wrong, the two sequences you mention are from the 1930s, so how can 1918 have been a recombinant of them?

[HenryN]

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

Maybe I'm being dense, but I am lost here. Unless I am reading it wrong, the two sequences you mention are from the 1930s, so how can 1918 have been a recombinant of them?

Over 90% of polymorphisms in 1918 can be found in the two H1N1 viruses (human and swine) from the 1930's (the two 1930's viruses represent what was circulating prior to 1918).

[wotan]

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

Over 90% of polymorphisms in 1918 can be found in the two H1N1 viruses (human and swine) from the 1930's (the two 1930's viruses represent what was circulating prior to 1918).

Now I don't get the last statement. How do we know they represent what was in circulation prior to 1918? If there is another thread where I can read up on that please direct me to it.

[HenryN]

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

<a rel="nofollow" href="http://www.recombinomics.com/News/07100901/H274Y_Fit.html">Commentary</a>

[AlaskaDenise]

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>

Commentary

Hong Kong Tamiflu Resistant Pandemic Sequence Released

Recombinomics Commentary 06:57
July 7, 2009

The NA sequence from the Hong Kong <a rel="nofollow" href="http://www.recombinomics.com/News/07040901/H274Y_Asymptomatic.html">teenager</a>with oseltamivir Tamiflu resistance, A/Hong Kong/2369/2009, has been released. The sequence is clearly that of pandemic H1N1 and exactly matches (other than H274Y) the sequence of an earlier isolate A/New Jersey/1/2009. Similarly, the HA sequence is also swine and has two recently acquired polymorphisms, one of which is also in New Jersey/1/2009. Thus this sequence is in circulation and as was seen in the isolates in Denmark and Japan, the H274Y is appended onto a swine H1N1 background.

These results mimic that seen in seasonal flu, where H274Y was appended onto multiple seasonal flu background. The polymorphisms jumped from one background to the next, via genetic hitchhiking and recombination. Thus like seasonal flu, the pandemic H1N1 has no evidence of reassortment. The H274Y is on an evolutionarily fit H1N1 that will allow the H274Y to move about through the pandemic H1N1 gene pool. This movement will be facilitated by widespread Tamiflu usage, which will select minor populations as happened in Denmark and Japan, where H274Y was identified in patients receiving a maintenance dose of Tamiflu.

However, in Hong Kong, like the many examples of H274Y in H1N1 seasonal flu, the resistance is in patients not receiving Tamiflu. However, the lessons of H274Y in seasonal flu were <a rel="nofollow" href="http://www.recombinomics.com/News/07030903/H274Y_Lessons.html">not learned</a>. Recent <a rel="nofollow" href="http://www.recombinomics.com/News/06290903/H274Y_Swine_Roche.html">comments</a> have described H274Y acquisitions through random mutation and reassortment. However, there has been no examples of recent seasonal H1N1 flu genes in the pandemic H1N1 sequences, and the H274Y in patients receiving Tamiflu likely represent selection of a minor population with H274Y that is silently spread. The release of the sequences from <a rel="nofollow" href="http://www.recombinomics.com/News/06290902/Pandemic_H1N1_Resistance.html">Denmark</a> and Japan would be useful.

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[AlaskaDenise]

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

<a rel="nofollow" href="http://www.recombinomics.com/News/07100901/H274Y_Fit.html">Commentary</a>

Commentary

Widespread Evolutionarily Fit Tamiflu Resistant Pandemic H1N1

Recombinomics Commentary 06:41
July 10, 2009

The NA sequence of the first pandemic isolate in Sapporo, Japan (A/Sopporo/1/2009) was released at Genbank today. Since Hokkaido's first report case was June 15, the isolate is relatively recent. It exactly matches the first isolate from New Jersey, A/New Jersey/1/2009, which was from a patient (22F) in Bergen county (see map) and collected in April. Both of these isolates match the California traveler who was tested at Hong Kong airport on June 11 and was found to be infected with oseltamivir resistant H1N1 (A/Hong Kong/2369/2009) based on H274Y, which was the only difference between the Hong Kong sequence and those form Bergen, New Jersey and Sopporo. The same sequence in these three locations indicates the evolutionarily fit H1N1 is widespread and has been circulating for months, but the number of pubic sequences remains low.

The Hong Kong, ex-San Francisco case was mild. The patient recovered without taking any antivirals, raising concerns that the resistance is circulating worldwide. The same genetic change, H274Y, has also been reported in patients receiving prophylactic levels of Tamiflu in Denmark and Osaka, Japan. The Osaka sequence, other than H274Y, matches multiple isolates from Japan, and is distinct from the Hong Kong/San Francisco/Sapporo/Bergen sub-clade. The sequence from Denmark has not been made public.

However, other countries are reporting suspect Tamiflu resistance in patients who have been treated for at least a month and are symptom free, but shed detectable H1N1. These reports raise concerns that H274Y is more widespread than the 3 confirmed cases and one presumed case in San Francisco.

The finding of H274Y in all confirmed cases raises concerns that the pattern in pandemic H1N1 will follow the pattern seen for seasonal flu, where H274Y increased to almost 100&#37; in the Brisbane/59 strain of seasonal flu. The spread of H274Y in the Brisbane strain was facilitated by the acquisition of key polymorphisms from the Hong Kong (clade 2C) strain of H1N1. However, H274Y had also been reported in clade 1 and clade 2c isolates from patients who were not receiving Tamiflu, and in countries where Tamiflu usage was low. The H274Y jumped from one sub-clade to another via genetic hitchhiking and recombination explained the pattern of acquisitions.'

The spread of H274Y in pandemic flu may be accelerated by widespread Tamiflu usage, levels approaching 100% in H1N1 seasonal flu, and the novel H1N1 reported in Canadian farm workers infected with an H3N2 triple reassortant that has acquired Brisbane/59 H1 and N1, with H274Y.

Thus, the detection of H274Y in pandemic H1N1 from patients who were and were not taking Tamiflu, as well as Brisbane N1 in H1N1 seasonal flu and H1N1 novel flu raises concerns that the levels of H274Y will markedly increase in the near term.

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[HenryN]

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

Now I don't get the last statement. How do we know they represent what was in circulation prior to 1918? If there is another thread where I can read up on that please direct me to it.

There is any sequence data prior to 1918 and the first H1 sequences are the ones I mentioned. On a phylogenetic tree, 1918 falls between the 1930 human and swine sequences. There was a Scientific American article on the 1918 virus several years ago, but I don't have the reference handy.

[HenryN]

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

There is any sequence data prior to 1918 and the first H1 sequences are the ones I mentioned. On a phylogenetic tree, 1918 falls between the 1930 human and swine sequences. There was a Scientific American article on the 1918 viruse several years ago, but I don't have the reference handy.

January, 2005

<a rel="nofollow" href="http://www.recombinomics.com/News/12140401/WSN33_1918_pandemic.html">Commentary</a>

[AlaskaDenise]

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

It is worth noting that 1918 was a recombinant between human A/WSN/33 and swine A/swine/Iowa/15/1930.

When looking at the A/H1N1 HAs from 1918 to 1939, one thing that jumps out in an alignment is that the WSN and W-S are so different than 1918 and from 1934 onward. What was so different about 1933?

added: I was just looking at human

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[HenryN]

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

When looking at the A/H1N1 HAs from 1918 to 1939, one thing that jumps out in an alignment is that the WSN and W-S are so different than 1918 and from 1934 onward. What was so different about 1933?

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WS/33 was the first human influenza isolated (isolated in William Smith's lab in 1933). WSN/33 was passed through mice and isolated from mouse brain (N stands for neurological).

1918 was associated with neurological problems, including long term in 1918 survivors.

[AlaskaDenise]

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

It is worth noting that 1918 was a recombinant between human A/WSN/33 and swine A/swine/Iowa/15/1930.

I just redid that alignment to include swine - what you say just jumps right out at you. Amazing. Obviously those swine sequences must have existed prior to 1918.

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[AlaskaDenise]

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

WS/33 was the first human influenza isolated (isolated in William Smith's lab in 1933). WSN/33 was passed through mice and isolated from mouse brain (N stands for neurological).

1918 was associated with neurological problems, including long term in 1918 survivors.

That answers a long standing question - that WSN is lab created and only W-S is natural. Thanks.

Very scarey genes there.

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[wotan]

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

January, 2005

<a rel="nofollow" href="http://www.recombinomics.com/News/12140401/WSN33_1918_pandemic.html">Commentary</a>

Thanks, gives me a lot to think about for awhile.