explanation of sequence letter codes
15 June 2006
niman – at 18:33
The sequences for HA in Indonesian H5N1 isolates came out today. Most have the H5N1 wild type cleavage site, RERRRKKR, but one, A/duck/Badung-Bali/05/2005(H5N1), has the Qinghai cleavage site GERRRKKR, as well as one of the polymorphisms in the Niger H5N1 (Qinghai-strain) sequence.
All reported Qinghai-strain isolates have PB2 E627K and the above isolate in Indonesia may be a source for E627K in Indonesia. It has been reported by Declan Butler to be in A/Indonesia/6/2005 and he has speculated that it is in H5N1 from the Sumatra cluster.
niman – at 18:36
There isolates at Los Alamos have the sequences encoding the Qinghai cleavage site
DQ447199 A/chicken/Egypt/960N3–004/2006 2006 H5N1 DQ406728 A/chicken/Nigeria/641/2006 2006 H5N1 AM231714 A/common pochard/France/06167/2006 2006 H5N1 DQ515984 A/Cygnus olor/Czech Republic/5170/2006 2006 H5N1 DQ435200 A/domestic cat/Iraq/820/2006 2006 H5N1 DQ435201 A/domestic goose/Iraq/812/2006 2006 H5N1 DQ659113 A/duck/Niger/914/2006 2006 H5N1 DQ464377 A/Egypt/2782-NAMRU3/2006 2006 H5N1 DQ435202 A/Iraq/207-NAMRU3/2006 2006 H5N1 DQ458992 A/mallard/Bavaria/1/2006 2006 H5N1 DQ449031 A/mallard/Italy/332/2006 2006 H5N1 DQ440535 A/swan/Iran/754/2006 2006 H5N1 DQ412997 A/swan/Italy/179/06 2006 H5N1 ISDN136919 A/swan/Italy/179/2006 2006 H5N1 AM236074 A/turkey/France/06222/2006 2006 H5N1 AB233319 A/bar-headed goose/Mongolia/1/05 2005 H5N1 DQ095621 A/Bar-headed Goose/Qinghai/12/05 2005 H5N1 DQ095617 A/Bar-headed Goose/Qinghai/5/05 2005 H5N1 DQ095612 A/Bar-headed Goose/Qinghai/59/05 2005 H5N1 DQ095615 A/Bar-headed Goose/Qinghai/60/05 2005 H5N1 DQ095618 A/Bar-headed Goose/Qinghai/61/05 2005 H5N1 DQ095620 A/Bar-headed Goose/Qinghai/62/05 2005 H5N1 DQ095622 A/Bar-headed Goose/Qinghai/65/05 2005 H5N1 DQ095623 A/Bar-headed Goose/Qinghai/67/05 2005 H5N1 DQ095613 A/Bar-headed Goose/Qinghai/68/05 2005 H5N1 DQ095619 A/Bar-headed Goose/Qinghai/75/05 2005 H5N1 DQ100554 A/black-headed goose/Qinghai/1/2005 2005 H5N1 DQ100555 A/black-headed goose/Qinghai/2/2005 2005 H5N1 DQ100556 A/black-headed gull/Qinghai/1/2005 2005 H5N1 DQ095616 A/Brown-headed Gull/Qinghai/3/05 2005 H5N1 DQ340848 A/chicken/Crimea/1/2005 2005 H5N1 DQ449632 A/chicken/Kurgan/05/2005 2005 H5N1 DQ323672 A/chicken/Kurgan/3/2005 2005 H5N1 DQ190859 A/chicken/Novosibirsk/64/05 2005 H5N1 DQ190860 A/chicken/Novosibirsk/65/05 2005 H5N1 DQ190861 A/chicken/Novosibirsk/66/05 2005 H5N1 DQ231242 A/chicken/Suzdalka/Nov-11/05 2005 H5N1 DQ231241 A/chicken/Suzdalka/Nov-12/05 2005 H5N1 DQ279301 A/chicken/Tula/10/2005 2005 H5N1 DQ389158 A/Cygnus olor/Astrakhan/Ast05–2−1/2005 2005 H5N1 DQ434889 A/Cygnus olor/Astrakhan/Ast05–2−10/2005 2005 H5N1 DQ343502 A/Cygnus olor/Astrakhan/Ast05–2−2/2005 2005 H5N1 DQ358746 A/Cygnus olor/Astrakhan/Ast05–2−3/2005 2005 H5N1 DQ363918 A/Cygnus olor/Astrakhan/Ast05–2−4/2005 2005 H5N1 DQ365004 A/Cygnus olor/Astrakhan/Ast05–2−5/2005 2005 H5N1 DQ364996 A/Cygnus olor/Astrakhan/Ast05–2−6/2005 2005 H5N1 DQ363923 A/Cygnus olor/Astrakhan/Ast05–2−7/2005 2005 H5N1 DQ399540 A/Cygnus olor/Astrakhan/Ast05–2−8/2005 2005 H5N1 DQ399547 A/Cygnus olor/Astrakhan/Ast05–2−9/2005 2005 H5N1 DQ449640 A/duck/Kurgan/08/2005 2005 H5N1 DQ190858 A/duck/Novosibirsk/56/2005 2005 H5N1 DQ230522 A/duck/Novosibirsk/56/2005 2005 H5N1 DQ320922 A/Environment/Qinghai/31/2005 2005 H5N1 DQ100557 A/great black-headed gull/Qinghai/1/2005 2005 H5N1 DQ095614 A/Great Black-headed Gull/Qinghai/2/05 2005 H5N1 DQ320919 A/migratory duck/Jiangxi/2136/2005 2005 H5N1 DQ320920 A/migratory duck/Jiangxi/2295/2005 2005 H5N1 DQ320921 A/migratory duck/Jiangxi/2300/2005 2005 H5N1 DQ453141 A/mute swan/Croatia/1/2005 2005 H5N1 DQ320137 A/swan/Astrakhan/1/2005 2005 H5N1 DQ231240 A/turkey/Suzdalka/Nov-01/05 2005 H5N1 DQ407519 A/turkey/Turkey/1/2005 2005 H5N1 AB233320 A/whooper swan/Mongolia/3/05 2005 H5N1 AB233321 A/whooper swan/Mongolia/4/05 2005 H5N1 AB233322 A/whooper swan/Mongolia/6/05 2005 H5N1 ISDN48972 A/Chicken/Hu bei/14/2004 2004 H5N1 AY830774 A/chicken/Macheng/2004 2004 H5N1
wetDirt – at 18:37
Congratualations on successfully predicting its presence from the dropped hints over the past weeks. Good job.
pogge – at 18:42
You may have noticed that we’re actively managing threads both for number and length in an effort to keep the site running well. The thread I moved your previous posts too was in fact the latest of a long line on the Indonesian clusters though it was renamed for that particular iteration. It seems to me that since this is another post on the same general subject, it can be moved there where the discussion can continue.
Closing this.
Edited to add:
I changed my mind for the moment. If you can think of a way to frame your opening post that both makes it general enough to serve for more than half a dozen posts and explains what you’re up to so we’ll know, I’d appreciate it.
DemFromCT – at 18:46
What is the significance, please, of one having GERRRKKR and the rest RERRRKKR?
(And would you prefer this be the thread for discussion? I’m seeing the same post multiple places.)
Thanks.
(The PB2 E627K seems important re its temperate compatability in the human nose. HA sequences are important for their receptor activity. Please correct the simplifications.)
wetDirt – at 18:52
And thanks, to G.N.Mahardika of Indonesia, for posting the sequences.
niman – at 19:00
pogge,
These really are two very different issues. The RESRRKKR thread is really on the cleavage site indicating the human H5N1 in Indonesia is from a source other than birds. That source remains unknown. The sequence for this thread was released today. It is the first sequence (human or bird) that has the Qinghai cleavage site, GERRRKKR.
There has been speculation that PB2 E627K is circulating in Indonesia. Declan Butler from Nature has indocated that PB2 E627K has been in Indonesia since the second case was reported in August 2005. Prior to his piece, I too had independently confirmed from an impeccable source that indeed E627K was in that isolate. Recently, Declan suggested that E627K was also in the Sumatra cluster, which would explain the lethality, as well as the neurological complications that were reported today in the sole surviving member of that Karo, Sumatra cluster.
The presence of the Qinghai cleavge site, as well as a polymorphism shared by another Qinghai sequence (from Niger) that was also just released, supports recombination between Qinghai and Indonesian H5.
The recombination requires a dual infection, so E627K could have been acquired by recombination or reassortment. However, no PB2 human sequences have been officially released, although sources indocate that the index case for the country, A/Indonesia/5/2005 has the bird version, while A/Indonesia/6/2005 has the human version.
The human version can increase the lethality and transmissibility of H5N1, so the presence of GERRRKKR in a bird is of interest, especially since the PB2 sequences are locked up in the WHO private data base.
niman – at 19:08
wetDirt, I suspect that posting Indonesian sequences prior to publication or “release” by whomever the buck is passed to next is NOT what WHO had in mind.
The publication of Indonesian sequence by a non-WHO affiliated lab is a welcome change.
PS, As a curious aside, rumor has it that there will soon be a paper published on H2H in Indonesia by the same people who have been denying H2H since August 2005.
DemFromCT – at 19:15
niman – at 19:00
Thank you.
pogge – at 19:42
Yes, thanks for the explanation. If I know from the opening post that there’s something to set a given thread apart from others, I’m a lot less likely to sweep it up in a house-cleaning.
BroncoBill – at 20:00
Dr. Niman---I have a question strictly from a layman’s point. What do the letters (such as GERRRKKR, etc.) mean? Are those the sequences you all are talking about? I promise I’ll only ask once :-)
niman – at 21:25
The letters for DNA is ATG&C. The aminio acids have three and one letter codes. For teh cleavges site the letters are
G=Glycine E=Glutamine R=Arginine K=Lysine S=Serine
There is free software to link up sequences or translate sequences using the toolbox here
http://www.ebi.ac.uk/Tools/sequence.html
All 64 codons for the 20 amnio acids are here
http://www.ebi.ac.uk/cgi-bin/mutations/trtables.cgi
I’ll paste it below, but it pribably won’t format. However, if you use the link abobe to see the “standard” table, you will see that C&T or A&G are redundant at the third position (same amino acid no matter if C/T is used or A/G is used.
H5N1 takes full advantage of thios redundancy. Almost all polymorphisms that are acquired from closely related sequences will be transitions (when flu recombines, it makes both versions - its a lot smarter than many trying to read the data).
VIEWER RESULTS
2nd
1st T C A G 3rd
T F Phe S Ser Y Tyr C Cys T
F Phe S Ser Y Tyr C Cys C
L Leu S Ser Ter Ter A
L Leu S Ser Ter W Trp G
C L Leu P Pro H His R Arg T
L Leu P Pro H His R Arg C
L Leu P Pro Q Gln R Arg A
L Leu P Pro Q Gln R Arg G
A I Ile T Thr N Asn S Ser T
I Ile T Thr N Asn S Ser C
I Ile T Thr K Lys R Arg A
M Met T Thr K Lys R Arg G
G V Val A Ala D Asp G Gly T
V Val A Ala D Asp G Gly C
V Val A Ala E Glu G Gly A
V Val A Ala E Glu G Gly G
niman – at 21:27
As expected, the formatting didn’t work, but the capital letter preceding the three letters is its abbreviation (F=Phe, S=Ser, Y-Tyr, etc).
BroncoBill – at 21:54
I think I got it. Thank you…
DemFromCT – at 22:04
BroncoBill – at 22:11
Thanks Dem…much appreciated. :-)
NS1 – at 23:14
Bill,
Sorry for the delay . . . pop this note with the others and it should start to make sense.
High Pathogenicity is generally found or correlated with a poly-basic cleavage site in H5N1.
Three aminos are considered basic.
- K = Lysine
- R = Arginine
- H = Histidine
When a string of these appears in the cleavage area (typically 5 to 6 of 8 aminos), a wider variety of protease products can cleave the gene segment.
Typically this allows for higher virulence and a wider number of organs that can be infected (multi-tropism).
16 June 2006
niman – at 02:50
I believe the proteases are specific for R and K (not H).
anonymous – at 04:17
I found no human H5N1-HA-sequences from Indonesia at:
http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/select.cgi
But 30 different avian sequences. The “Grandmother” (center,min.total differences)
of all Indonesian sequences being A/Ck/Indonesia/BL/2003(H5N1).
Qinghai-strain Grandmother is A/Bar-headed Goose/Qinghai/59/05(H5N1).
differences to grandmother:
Qinghai:1–14, average 6.94 (32 sequences)
Indonesia:2–24, average 12.41 (30 sequences)
distance GMQinghai-GMIndonesia=34
{difference=distance=number of mutations}
Nigeria was surprisingly close to Kurgan/3 (d=4) , d(GM)=5
d(Niger,Niogeria)=11,d(Niger,Kugan_duck)=8,d(Niger,Kurgan/3=11),d(Niger,GM)=6
you could speculate Niger was introduced by smuggling a Kurgan-like chicken,
but Niger is not so different, i.e. when you take into account that it was a duck. Egypt however is pretty distant from both and from GM.
That speaks against the migratory route Kurgan-Turkey-Egypt-Nigeria
anonymous – at 04:20
typo correction: d(Nigeria,GMQinghai)=7
NS1 – at 05:35
Niman,
No question about that in this virus. Just mentioned the Histidine because it is considered basic. We both see that its not really featured in these matters.
NS1 – at 05:37
gs-
Good work on the study.
Remember that we are woefully short of sequences and specimens, so your analysis may not allow conclusions.
anonymous – at 05:57
don’t call me gs.
niman – at 08:17
gsgs, The similarity between Nigeria and Kurgan HA sequences was described in March when the sequence came out. The Indonesian human HA sequence is at Los Alamos. Sequences with ISDN numbers are from the WHO private repository that have been released to the public side.
17 June 2006
niman – at 04:55
Here is the updated version of Los Alamos sequences coding for GERRRKKR:
DQ661910 A/chicken/Afghanistan/1207/2006 2006 H5N1
DQ447199 A/chicken/Egypt/960N3–004/2006 2006 H5N1 DQ676834 A/chicken/Krasnodar/01/2006 2006 H5N1 DQ676830 A/chicken/Mahachkala/05/2006 2006 H5N1 DQ406728 A/chicken/Nigeria/641/2006 2006 H5N1 AM231714 A/common pochard/France/06167/2006 2006 H5N1 DQ515984 A/Cygnus olor/Czech Republic/5170/2006 2006 H5N1 DQ435200 A/domestic cat/Iraq/820/2006 2006 H5N1 DQ435201 A/domestic goose/Iraq/812/2006 2006 H5N1 DQ659113 A/duck/Niger/914/2006 2006 H5N1 DQ464377 A/Egypt/2782-NAMRU3/2006 2006 H5N1 DQ435202 A/Iraq/207-NAMRU3/2006 2006 H5N1 DQ458992 A/mallard/Bavaria/1/2006 2006 H5N1 DQ449031 A/mallard/Italy/332/2006 2006 H5N1 DQ440535 A/swan/Iran/754/2006 2006 H5N1 DQ412997 A/swan/Italy/179/06 2006 H5N1 ISDN136919 A/swan/Italy/179/2006 2006 H5N1 AM236074 A/turkey/France/06222/2006 2006 H5N1 AB233319 A/bar-headed goose/Mongolia/1/05 2005 H5N1 DQ137873 A/bar-headed goose/Qinghai/0510/05 2005 H5N1 DQ095621 A/Bar-headed Goose/Qinghai/12/05 2005 H5N1 DQ095617 A/Bar-headed Goose/Qinghai/5/05 2005 H5N1 DQ095612 A/Bar-headed Goose/Qinghai/59/05 2005 H5N1 DQ095615 A/Bar-headed Goose/Qinghai/60/05 2005 H5N1 DQ095618 A/Bar-headed Goose/Qinghai/61/05 2005 H5N1 DQ095620 A/Bar-headed Goose/Qinghai/62/05 2005 H5N1 DQ095622 A/Bar-headed Goose/Qinghai/65/05 2005 H5N1 DQ095623 A/Bar-headed Goose/Qinghai/67/05 2005 H5N1 DQ095613 A/Bar-headed Goose/Qinghai/68/05 2005 H5N1 DQ095619 A/Bar-headed Goose/Qinghai/75/05 2005 H5N1 DQ100554 A/black-headed goose/Qinghai/1/2005 2005 H5N1 DQ100555 A/black-headed goose/Qinghai/2/2005 2005 H5N1 DQ100556 A/black-headed gull/Qinghai/1/2005 2005 H5N1 DQ095616 A/Brown-headed Gull/Qinghai/3/05 2005 H5N1 DQ340848 A/chicken/Crimea/1/2005 2005 H5N1 DQ676838 A/chicken/Dovolnoe/03/2005 2005 H5N1 DQ449632 A/chicken/Kurgan/05/2005 2005 H5N1 DQ323672 A/chicken/Kurgan/3/2005 2005 H5N1 DQ190859 A/chicken/Novosibirsk/64/05 2005 H5N1 DQ190860 A/chicken/Novosibirsk/65/05 2005 H5N1 DQ190861 A/chicken/Novosibirsk/66/05 2005 H5N1 DQ231242 A/chicken/Suzdalka/Nov-11/05 2005 H5N1 DQ231241 A/chicken/Suzdalka/Nov-12/05 2005 H5N1 DQ279301 A/chicken/Tula/10/2005 2005 H5N1 DQ389158 A/Cygnus olor/Astrakhan/Ast05–2−1/2005 2005 H5N1 DQ434889 A/Cygnus olor/Astrakhan/Ast05–2−10/2005 2005 H5N1 DQ343502 A/Cygnus olor/Astrakhan/Ast05–2−2/2005 2005 H5N1 DQ358746 A/Cygnus olor/Astrakhan/Ast05–2−3/2005 2005 H5N1 DQ363918 A/Cygnus olor/Astrakhan/Ast05–2−4/2005 2005 H5N1 DQ365004 A/Cygnus olor/Astrakhan/Ast05–2−5/2005 2005 H5N1 DQ364996 A/Cygnus olor/Astrakhan/Ast05–2−6/2005 2005 H5N1 DQ363923 A/Cygnus olor/Astrakhan/Ast05–2−7/2005 2005 H5N1 DQ399540 A/Cygnus olor/Astrakhan/Ast05–2−8/2005 2005 H5N1 DQ399547 A/Cygnus olor/Astrakhan/Ast05–2−9/2005 2005 H5N1 DQ644959 A/duck/Badung-Bali/05/2005 2005 H5N1 DQ449640 A/duck/Kurgan/08/2005 2005 H5N1 DQ190858 A/duck/Novosibirsk/56/2005 2005 H5N1 DQ230522 A/duck/Novosibirsk/56/2005 2005 H5N1 DQ320922 A/Environment/Qinghai/31/2005 2005 H5N1 DQ676840 A/goose/Krasnoozerka/627/2005 2005 H5N1 DQ212792 A/goose/Novosibirsk/4/2005 2005 H5N1 DQ100557 A/great black-headed gull/Qinghai/1/2005 2005 H5N1 DQ095614 A/Great Black-headed Gull/Qinghai/2/05 2005 H5N1 DQ230521 A/grebe/Novosibirsk/29/2005 2005 H5N1 DQ190857 A/grebe/Novosibirsk/29/2005 2005 H5N1 DQ320919 A/migratory duck/Jiangxi/2136/2005 2005 H5N1 DQ320920 A/migratory duck/Jiangxi/2295/2005 2005 H5N1 DQ320921 A/migratory duck/Jiangxi/2300/2005 2005 H5N1 DQ453141 A/mute swan/Croatia/1/2005 2005 H5N1 DQ320137 A/swan/Astrakhan/1/2005 2005 H5N1 DQ231240 A/turkey/Suzdalka/Nov-01/05 2005 H5N1 DQ407519 A/turkey/Turkey/1/2005 2005 H5N1 AB233320 A/whooper swan/Mongolia/3/05 2005 H5N1 AB233321 A/whooper swan/Mongolia/4/05 2005 H5N1 AB233322 A/whooper swan/Mongolia/6/05 2005 H5N1 ISDN48972 A/Chicken/Hu bei/14/2004 2004 H5N1 AY830774 A/chicken/Macheng/2004 2004 H5N1
anonymous – at 05:55
GERRRKKR is just characteristic for the Qinghai strain. Can you list the sequences with GERRRKKR but not from the Qinghai strain ? And the sequences from the Qinghai strain which have not GERRRKKR. That should be much smaller lists and easier to comprehend. Thanks.
niman – at 06:40
The isoaltes that are not Qinghai are at the bottom of the list (migratory birds from Jiangxi and chickens from Hubei and Macheng).
There is one Mongolian isolate with GERRRRKR and the Ian Brown presentation has some additional novel cleavage sites, but he has only released one sequence (turkey/Turkey/1/2005) and did not specific which isoaltes in Europe had the novel sites).
niman – at 06:41
Comments on Qinghai in Bali.
20 June 2006
MaMa- Still open – at 01:06
Mr White42 – at 10:16
bump
niman – at 10:39
The above commentray has three long lists of isolates with Qinghai polymorphisms with Indonesian sequences bolded for easy analysis.
20 July 2006
NgurahfromBali – at 19:57
Hi All, The author of the GeneBank data of Indonesian isolates was me. I do not think that the present of Qinghai cleavage site from Bali is an indicator of a recombination. As the virus A/duck/Badung-Bali/05/2005(H5N1)shows its nature as ‘an Indonesian virus’, the cleavage site of Qinghai seems a reflection of mutagenicity of influenza virus.
niman – at 20:14
NgurahfromBali,
Welcome to FW!
All piblished isolates from Indonesia, including A/duck/Badung-Bali/05/2005 have an Indonesian genetic background (as seen in this phylogentic tree. However, they have some polymoprhisms that match Qingai, including the above isolate. These look like point mutations, but the pattern of these aquisitions point toward recombination resulting in the acquistion of a very small region, that frequently only has one nucleotidde change, so it looks like a point mutation.
As you know, the cleavage site in most human isolates from Indonesia have the RESRRKKR sequence. Have you found this in any of the avian isolates in Bali (or anywhere in Indonesia)? As you know, all of the human cases in Indonesia have been identified in the past 12 months, but most of the published sequences from birds are from 2005 or earlier.
TreasureIslandGal – at 20:22
Welcome to the fluwikie NgurahfromBali.
We would love to have you visit us often to shed some light on what is happening with the virus as far as mutations go. Although we all understand that you are not permitted to actually list sequence data, you may be abel to at least comment on overall indications of changes and mutations that you may be seeing as this thing ravages Indonesia.
Speaking for everyone on this board, we all sympathize with the Indonesian people through this difficult time of natural disasters that they seem to be afflicted by. We wish everyone could be safe and send our condolences to all families who have lost loved ones between the volcano, earthquakes, tsunamis and BF instances. -as well as the many other problems suffered there like Dengue, Malaria, etc etc etc
Tom DVM – at 20:27
NgurahfromBali. Welcome.
TreasureIslandGal. That was a beautiful piece of writing. Thanks.
Thinlina – at 21:35
About the feline (cat) sequences: isn’t it quite usual to eat cats and dogs in East Asia?
Tom DVM – at 21:41
Thinlina. I’m pretty sure you are right about the dogs…but I have not heard of eating cats.
Thinlina – at 21:46
A few years ago there was a TV document about the Far Eastern gastronomique… They showed how dogs and cats were sold for cuisine meat on the market places.
Tom DVM – at 21:48
Thinlina. Then I stand corrected. It is a very important issue that you raise…another possible mode of infection and as well many other mammals eat dogs and cats as well…that may be part of the problem with our friendly and highly intelligent ominivore and close relative…the pig.
21 July 2006
NgurahfromBali – at 09:10
Tom DVM Agree with you on the possible role of pig. One small step TO Man (via pig), one giant leap to mankind. I am working hard in detecting the H5N1-devil in pig as an EWS (early warning system) for potential “flu tsunami”.
niman – at 09:31
NgurahfromBali,
The pig or other mammal is a logocal choice, but I was actually asking about additional evidence in birds of an HA cleavage site, RESRRKKR, that matches the vast majority of human cases. I believe 100 bird samples were recently sent to Australia fr analysis and as of June of this year, there was no acknowledgement of RESRRKKR in birds. There was a rumor that one such bird isolate was found south of Jakarta, but I haven’t seen that result published anywhere, and was wondering if you had heard anything about anyone finding RESRRKKR in any source other than human and cat.
The Sarge – at 09:54
Dr. Niman (or anyone)
I understand that the multiple basic residues in the HA0 cleavage site opens it up for mutltiple and ubiquitous proteases. This in turn leads to wider tissue tropism, multi-organ involvement and more serious consequences.
What should I be looking for in the posts and news that would indicate a change in the HA binding domain - one that would show a change of ‘preference’ from the avian 2,3 sialic acid receptor to the human 2,6 receptor.
Or, has the importance of 2,3 vs. 2,6 become so muddy that we don’t consider it much? I rarely see it discussed anymore.
Thanks!
NgurahfromBali – at 10:04
Dr Niman, All my viruses show RERRRKKR motive. No news on ‘human motive’. I have a limitation to access sequence data. I will keep searching.
NgurahfromBali – at 10:17
The Sarge, I propose to this forum, 2,3 vs 2,6 is hypothetical. It is not a dogma. Leave the dogma in bible, qoran, veda.
Any comment?
Tom DVM – at 10:22
NgurahfromBali. I think as time goes on, we will find that there are more similarities between humans and birds then differences.
I’m not sure that H5N1 is as aware of its inability to infect humans as humans appear to be.
I think it is good to continue to explore these issues from every concievable angle but I am with Dr. Niman on the fact that researchers should at all times keep in the back of their minds,that the what is discovered in a lab (in vitro) often has little relation to what goes on in nature (in vivo).
By the way, your question hits on the crux of the matter.
Thinlina – at 11:11
Just wanted to share a few links with you..:
http://messybeast.com/eat-cats.htm http://www.capital.net/com/phuston/cateating.html http://www.saveacat.org/acr_articles/asiancats.htm http://asiarecipe.com/chidine.html
Thinlina – at 11:14
There is four different links. Dont know why thei look as if there was only two :/
Thinlina – at 11:26
“An estimate by the Yangcheng Evening News suggests that a cat stall in the game-meat market can easily sell 300–400 kilograms of cat meat daily in winter. There are about 80 stalls selling cats in the three [game meat] markets. This adds up to 10,000 cats a day.”
And yes, Niman, I understood you, but got interested to search a little this cat-eating idea.
niman – at 11:41
The Sarge, You should look for dead people.
niman – at 11:46
NgurahfromBali, Have you loked at any 2006 sequences? The first human sequence was about a year ago and most of the human H5N1 sequences listed are from late 2005 and 2006. Available bird sequences from Indonesia include 2005, but I have not seen any 2006 bird H5N1 sequences from Indonesia.
NgurahfromBali – at 12:23
Dr Niman, I have partial HA of 2006 sequence from animal. It still keep RERRRKKR motive.
Hillbilly Bill – at 12:30
niman – at 11:41
If that wasn’t so morbid, it would be hilarious! I didn’t know you had such a sense of humor Dr. Niman.
The Sarge – at 13:06
NgurahfromBali and Dr. Niman:
Thank you. I agree with Dr. Niman that the only measure that matters, unfortunately, is dead folks. My opinion is that there may soon be far too many of these, already so in Indonesia.
It is just that discussions of the HA binding domain seem to dominate so much of the literature over the past decade. However, there recently seems to have been a lot of doubt raised about the importance or even validity of the isomer ‘preference’ as an indicator/determinant of host range restriction and pathogenesis. I just wanted to see if that was your impression also.
The more we learn, it seems, the more we don’t know - or maybe more accurately, the more we find out that what we know just isn’t so.
Sort of props open the door for Henry, no?
niman – at 13:19
The Sarge, I believe that the only two changes that WHO woudl abnnounce would be reassortment involving a human or swine gene and a change in the receptor binding domain.
The Sarge – at 13:43
Since the binding domain is a 3-dimensional protein structure, and its affinity - as I am geiven to understand it - is a function of that physical structure (as opposed to a chemical interaction, as with proteases), we have to be concerned with the secondary and tertiary folding. What can the sequences for the HA gene tell us about structure of the proteins they are encoding, if anything. IOW - can the sequences inform us as to course of development of the HA binding domain, or must this be observed after the fact via x-ray crystallography or similar methods?
Thanks!
The Sarge – at 18:44
Bump, cause I’d really like to know.
Jefiner – at 20:11
bump
niman – at 20:16
Then two key positions are 226 and 228. The story is in the sequence.
22 July 2006
a’Akova – at 01:58
NgurahfromBali – at 09:10 on 21 July:
“One small step TO Man (via pig), one giant leap to mankind.”
Clever, especially since 21 July is the anniversary of mankind’s first step on the moon!
a’Akova – at 02:17
“However, which mutations are likely to modulate receptor specificity in the H5 serotype is not so obvious.”
“Although a dramitic switch to a classic [alpha]2–6 human receptor binding was not observed(51), the double mutant (Q226L, G228S) showed sunstantially reduced affinity to [alpha]2–3 sialosides), as noted for the mutants of the H3 A/Hong Kong/156/1997 virus(52). But it was notable that significant binding to a natural, branched [alpha]2–6 biantennary glycan (nos. 56 and 57) was observed for both the double mutant and the single G228S mutant (Fig 5H).”
J. Stevens, et al., Science 312, 404 (2006).
Dr. Nimian states 226 and 228 with certainty, a cite with more information would be appreciated.
The Sarge – at 13:07
Thanks a’Akova and Dr. Niman!
anonymous – at 14:00
see also this picture posted by Alaska Denise:
http://www-ermm.cbcu.cam.ac.uk/01003489h.htm
28 October 2006
Closed - Bronco Bill – at 20:15
Closed to maintain Forum speed.