H5N1 HA sequence - implications for human transmission

[Toaster2]

I posted this at (another site) - thought it might be relvant to repost here.


H5N1 HA sequence - implications for human transmission

A.A. in binding site (aa)................?human? mutations............Relevance

98 (Y) .................................................. ....... .....................Not relevant
(101) (D in avH5).................................D in avH5 ..................relevance not clear
133a (only in avH5)............................S or L in avH5...............relevance not clear
134 (only in avH5)............................................. ..................relevance not clear
135 (G in huH3, T swiH9, V avH5).........V135G or V135T.............may be relevant
136 (S)............................................... ....... .......................Not relevant
137 (N in huH3, K swiH9, S avH5)..........S137N or S137K............may be relevant
153 (W)............................................... ....... ......................Not relevant
155 (T in huH3, T swiH9, I avH5)...........I155T/I155V(a2,6)......may be relevant
156 (K only in human H3 ? a2,6)...............?156K.......................re levance not clear
158 (G only in human H3 - a2,6)...............?158G......................relevance not clear
(159) ..............................................?159N (a2,6)................relevance not clear
(179)............................................. ....... .............................relevance not clear
183 (H in hu H3, avH5)..........................is already in H5.............relevance not clear
189 (A in H5, Q in huH3 = a2,3 spec)........is already not Q...........relevance not clear
190 (E huH3+avH5,VswH9+DhuH1)......E190D or E190V..........Highly relevant
(192) (T in Av H5) .................................................. ..............relevance not clear
193 (S in huH3, N swiH9, R avH5).............R193S R193N...............relevant
225 (G in huH3 + swiH9 ? a2,3sp)........G225D (+E190D ?).......Highly relevant
226 (L in Hu H3, L swiH9, Q avH5)........Q226L (no E190D?).......Highly relevant
(227) (S avian, N human)....................S227N (S227N).............Relevant
228 (S in huH3)..................................G228S (no E190D?).......Highly relevant


OK, some more info. This table is based on :

A) the crystal structure of avian H5 (compared to human H3 and swine H9)
B) the sugar specificity (a2,3 is avian intestine specificity - a2,6 is mammalian airway)
c) the amino acids known to change avian H1 and H3 into human H1 and H3
d) pos 98,136 and 153 are conserved between H3, H5 and H9 and I have therefore considered them as not relevant for mutation as these mutations might disturb the binding to much.
It should give a good indication as to which mutations could be considered to be relevant to watch. Only amino acids known to be in the HA binding site are listed - amino acids between brackets are close but may not make direct contact in the binding site.

THIS IS BY NO MEANS A DEFINITIVE TRUTH OR PANDEMIC PROJECTION _ JUST MY ANALYSIS BASED ON THE LITERATURE AND COMMON SENSE !!!

[CGB]

Re: H5N1 HA sequence - implications for human transmission

Thank you Toaster2. Do you know which of these sequences may be most evident in Africa at this time? Many of the migratory birds will be returning from Africa to Europe in the Spring. I was wondering which sequences to watch for from Africa.

[GaudiaRay]

Re: H5N1 HA sequence - implications for human transmission

Another posting by Toaster2, with his permission:

I analysed a couple of papers from the scientific literature. One is very informative on the structure of avian H5 (in comparison with human H3 and swine H9) - this paper is available online as PDF and shows the contact residues in the HA binding sites for a synthetic a2,3 and a2,6 :

Ha Y, Stevens DJ, Skehel JJ, Wiley DC. X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs.
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11181-6. Epub 2001 Sep 18.

The other key paper is not available online, but I do have access to it. This paper shows the effects of substitutions in the binding site of H1 and H3 human HA:
Stevens J, Blixt O, Glaser L, Taubenberger JK, Palese P, Paulson JC, Wilson IA. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities.
J Mol Biol. 2006 Feb 3;355(5):1143-55. Epub 2005 Nov 18.

Then there are several other papers I took into account, and tried to extrapolate data from H1, H3 and H9 to the known contact residues of H5. I think the overview is pretty accurate but I do not think it is totally complete (these things never are - that is why it may need updating now and then).

[gsgs]

Re: H5N1 HA sequence - implications for human transmission

positions 98,136,153,155,183,190,194,195,224,225,226,227,228
were identified as critical wrt. HA-receptor binding

[gsgs]

Re: H5N1 HA sequence - implications for human transmission

> Last edited by Admin : 03-22-2006 at 10:38 AM. Reason: deleted url

hi Admin, which url was deleted and why ?

[gsgs]

Re: H5N1 HA sequence - implications for human transmission

I posted a list of the variations in the receptor
binding domains here:

http://www.flutrackers.com/forum/showthread.php?t=3547