Identification of Dual Receptor-binding Specific Strains of Human H5N1 Viruses in China

[tetano]

Biomed Environ Sci. 2012 Feb;25(1):104-8.
Identification of Dual Receptor-binding Specific Strains of Human H5N1 Viruses in China.
Zhou JF, Zou SM, Li Z, Wang M, Dong J, Guo JF, Wei HJ, Wen le Y, Xu H, Shu YL.
Source

State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
Abstract
OBJECTIVE:

Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-linked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China.
METHODS:

The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell (CRBC) agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers.
RESULTS:

Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains: A/Guangdong/1/06 (A/GD/1/06) and A/Guangxi/1/08 (A/GX/1/08). Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses.
CONCLUSION:

The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.

Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

PMID:
22424634
[PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/22424634

 

[sharon sanders]

Re: Identification of Dual Receptor-binding Specific Strains of Human H5N1 Viruses in China

hat tip Michael Coston


Study: Dual Receptor Binding H5N1 Viruses In China




(Very Simplified Illustration of RBDs)
# 6238


Human adapted influenza viruses have an RBD - Receptor Binding Domain (the area of its genetic sequence that allows it to attach to, and infect, host cells) that – like a key slipping into a padlock -`fit’ the receptor cells commonly found in the human upper respiratory tract; the alpha 2,6 receptor cell.

Avian adapted flu viruses, like the H5N1 virus, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds.
​

While there are some alpha 2,3 cells deep in the lungs of humans, for an influenza to be successful in a human host, it needs to a able to bind to the a 2,6 receptor cell.

A design flaw that - at least for the time being – is believed to have kept the H5N1 virus from taking off in the human population (note: there are likely other genetic barriers as well).
​

All of which serves as prelude to a study out of China where researchers have found at least two strains of the H5N1 virus that demonstrated the ability to bind to both a2,3 and a2,6 receptor cells.

Before anyone starts to head down to the bunker, these viruses were collected between 2003 and 2009, and despite their ability to bind to human-type receptors (at least at high viral loads), they have not managed to spark a pandemic.
​

The following excerpts come the abstract that appears in Biomedical and Environmental Sciences, Volume 25, Issue 1(h/t Tetano on FluTrackers for this link).
Follow the link to read it in its entirety.

Identification of Dual Receptor-binding Specific Strains of Human H5N1 Viruses in China

Jian Fang ZHOU, Shu Mei ZOU, Zi LI, Min WANG, Jie DONG, Jun Feng GUO, He Jiang WEI, Le Ying WEN, Hong XU, Yue Long SHU
Abstract (excerpts):


<snip></snip>


Results Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains: A/Guangdong/1/06 (A/GD/1/06) and A/Guangxi/1/08 (A/GX/1/08). Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses.
Conclusion The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.
​

While a significant step towards adaptation to human hosts, obviously something more is needed to make the H5N1 virus a pandemic threat.

Lest anyone be too comforted, this study does show that the H5N1 virus is capable of evolving towards a more `humanized’ pathogen.
​

Which is why the world remains at pre-pandemic Phase III on the H5N1 virus, and we continue to watch for signs of better adaptation to humans.



Posted by Michael Coston at 7:37 AM