Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

[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.

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

[Toaster2]

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

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.

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.

[HenryN]

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.

[HenryN]

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.

[HenryN]

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

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.

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).

[AlaskaDenise]

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)

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

YYY
. . .
F . .
. . .

(added: starting in position 274)

.

[HenryN]

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"?



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

YYY
. . .
F . .
. . .

(added: starting in position 274)

.

F is phenylalanine, is upstream, and is in H1 seasonal flu.

[AlaskaDenise]

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

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...........

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.

.

[HenryN]

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

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.

.

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.

[HenryN]

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>

[HenryN]

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

Tamiflu-resistant swine flu strain emerges


NZPA July 9, 2009, 6:32 am

<?XML:NAMESPACE PREFIX = YGG /><YGG:ENTITY id=t2 ref="#WH7btmgY3RG1aCOGXWfsEA">New Zealand</YGG:ENTITY> health officials hope the diagnosis of a San Francisco teenager with a Tamiflu-resistant strain of swine flu is a random mutation of the virus.

"We will be asking the Pandemic Influenza Technical Advisory Group (PITAG) to have a look at this," deputy director of public health Fran McGrath told NZPA.
She hoped it would turn out to be a "point mutation" of the virus -- which can occur in a patient even if they are not taking the anti-viral drug.
The Health Ministry would ask its technical experts to talk to virologists and other specialists at the Centres for Disease Control, in the United States, "about any evidence of the sort that we're going to be worried about", she said.
There were two main possibilities: either the case in the 16-year-old American girl showed swine flu was capable of not only developing drug resistance but also spreading between humans in that resistant form, or it was a one-off point mutation.
Two other cases of swine flu resistant to Tamiflu had occurred in patients taking the drug in <YGG:ENTITY id=t3 ref="#GgLXtmgY3RG1aCOGXWfsEA">Japan</YGG:ENTITY> and Denmark, but Dr McGrath said it would be good if the virus had not yet mutated to a form which could spread carrying the mutation.
"So far, these are looking like point mutations, which is good news," she said.
Arthur Reingold, a professor at the University of California's school of public health, told the San Francisco Chronicle the fact the teenager was not taking Tamiflu suggested she may have caught the resistant variant from somebody else.
But Dr McGrath said it was important to remember that the virus spreading in <YGG:ENTITY id=t4 ref="#WH7btmgY3RG1aCOGXWfsEA">New Zealand</YGG:ENTITY> was still capable of being treated with Tamiflu.
Since January 2008 seasonal A (H1N1) flu viruses have become resistant to Tamiflu.
So far, six samples of the swine flu A (H1N1) viruses have also been tested, and none had the mutation, which indicated they were still sensitive to the drug.
<YGG:ENTITY id=t5 ref="#WH7btmgY3RG1aCOGXWfsEA">New Zealand</YGG:ENTITY> had a fair way to go before having to deal with a resistant form with good transmissibility, but when that happened the next step would be to switch to another anti-viral, such as Relenza.
Dr McGrath said the factor which would influence any use of swine flu vaccine in NZ would be the pattern of infections and their severity.
"Right at the moment, there isn't a lot of reason why we'd want to short-circuit the normal licensing process," she said.
"Severity would be the key factor."
Two <YGG:ENTITY id=t6 ref="#WH7btmgY3RG1aCOGXWfsEA">New Zealand</YGG:ENTITY> scientists have said in a study published in the journal Eurosurveillance that the present form of swine flu may be at least 40 times less lethal than originally estimated.
Probably no more than one in 10,000 patients might die, and the toll might be as low as one in 1 in 100,000 patients, according to Nick Wilson and Michael Baker.
Prime Minister John Key said this week that the Government had ordered a stockpile of a new swine flu vaccine for healthcare staff and other emergency workers.
The Government has ordered 300,000 doses of a vaccine from Baxter Healthcare -- enough to give 150,000 people the required two doses -- and it will be delivered within a month.
But the licensing of the vaccine is likely to take until December.
The death of a Christchurch man yesterday took the total number of swine flu deaths in <YGG:ENTITY id=t7 ref="#WH7btmgY3RG1aCOGXWfsEA">New Zealand</YGG:ENTITY> to five.
Chief Coroner Neil MacLean said the 49-year-old victim, who was thought to have underlying respiratory problems, died at the weekend.
A 46-year-old Blenheim man who died at his home a week ago was the country's fourth linked death, said Dr McGrath.
"While he has tested positive for novel influenza A, he had pre-existing medical conditions," she said.
The number of confirmed cases of swine flu yesterday was 1272, but Dr McGrath said this was only a small sampling of the actual number of cases.

http://nz.news.yahoo.com/a/-/top-stories/5713050/tamiflu-resistant-swine-flu-strain-emerges/

[HenryN]

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

NA sequence of Osaka/1 matches New Jersey/1 (which matches Hong Kong prior to acquistion of H274Y).

[gsgs]

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

add 1 for normal numbering, so it's H275Y

[HenryN]

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

add 1 for normal numbering, so it's H275Y

Just about everyone uses H274Y except Japan. Its the same change as H5N1, where it is also called H274Y.

[HenryN]

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

HA travel log for Sapporo/1

gb|GQ365446.1| Influenza A virus (A/Sapporo/1/2009(H1N1)) seg... 40.1 0.047
gb|FJ231773.1| Influenza A virus (A/Rheinland-Pfalz/58/2005(H... 40.1 0.047
gb|CY040170.1| Influenza A virus (A/Puerto Rico/8-SV14/1934(H... 40.1 0.047
gb|CY038903.1| Influenza A virus (A/Puerto Rico/8-SV3/1934(H1... 40.1 0.047
gb|CY038895.1| Influenza A virus (A/Puerto Rico/8-SV1/1934(H1... 40.1 0.047
gb|CY034132.1| Influenza A virus (A/WSN/1933(H1N1)) segment 4... 40.1 0.047
gb|CY033577.1| Influenza A virus (A/Puerto Rico/8/1934(H1N1))... 40.1 0.047
gb|CY032213.1| Influenza A virus (A/swine/Wisconsin/1/1961(H1... 40.1 0.047
gb|EF190982.1| Influenza A virus (A/lvPR8/34(H1N1)) segment 4... 40.1 0.047
gb|EF190974.1| Influenza A virus (A/hvPR8/34(H1N1)) segment 4... 40.1 0.047
gb|CY020469.1| Influenza A virus (A/Phila/1935(H1N1)) segment... 40.1 0.047
gb|CY020445.1| Influenza A virus (A/Henry/1936(H1N1)) segment... 40.1 0.047
gb|EF467821.1| Influenza A virus (A/Puerto Rico/8/34(H1N1)) s... 40.1 0.047
gb|CY019955.1| Influenza A virus (A/Alaska/1935(H1N1)) segmen... 40.1 0.047
gb|CY010788.1| Influenza A virus (A/WSN/1933 TS61(H1N1)) segm... 40.1 0.047
gb|DQ508905.1| Influenza A virus (A/Wilson-Smith/1933(H1N1)) ... 40.1 0.047
gb|CY009604.1| Influenza A virus (A/Wilson-Smith/33(H1N1)) se... 40.1 0.047
gb|CY009444.1| Influenza A virus (A/Puerto Rico/8/34(H1N1)) s... 40.1 0.047
gb|J02176.1|FLAHAMY Influenza A virus (A/WSN/33) hemagglutini... 40.1 0.047
gb|CY009324.1| Influenza A virus (A/Melbourne/35(H1N1)) segme... 40.1 0.047
gb|AF389118.1| Influenza A virus (A/Puerto Rico/8/34/Mount Si... 40.1 0.047
gb|AF408861.1|AF408861 Influenza A virus (A/NWS-Mvi(H1N2)) he... 40.1 0.047
gb|AF408860.1|AF408860 Influenza A virus (A/NWS-Tokyo(H1N2)) ... 40.1 0.047
gb|AF408859.1|AF408859 Influenza A virus (A/NWS-G70c(H1N9)) h... 40.1 0.047
emb|Z54287.1| Influenza A virus (Mongolia/153/88 (H1N1)) RNA ... 40.1 0.047
emb|Z54288.1| Influenza A virus (A/Mongolia/111/91 (H1N1)) RN... 40.1 0.047
emb|X57493.1| Influenza A virus (A/swine/Illinois/63(H1N1)) H... 40.1 0.047
emb|V01088.1| Influenza A virus (A/PR/8/34(HON1)) hemagglutin... 40.1 0.047
gb|AF091307.1|AF091307 Influenza A virus (A/swine/Wisconsin/1... 40.1 0.047
gb|U38242.1|IAU38242 Influenza A virus (A/Tokyo/3/1967(H1)) h... 40.1 0.047
gb|U37727.1|IAU37727 Influenza A virus (A/NWS/G70C(H1N9)) hem... 40.1 0.047
gb|U08904.1|IVU08904 Influenza virus A/WS/33 (H1N1) haemagglu... 40.1 0.047
gb|U08903.1|IVU08903 Influenza virus A/NWS/33 (H1N1) haemaggl... 40.1 0.047