…Elsevier’s Virology was calmly publishing another paper on a “mutant” H5N1….
Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans. [my emphasis – Ed]
I have covered the use of glycan arrays to characterise influenza viruses’ binding specificity previously; I thought then, and do now, that it is a very cool technology – and one that has shown in this case that H5N1 variants can be selected from an originally “wild” population, that preferentially bind the human-type receptor.
And they did it like this:
To examine the functional evolution of H5 HA receptor specificity in the laboratory, we implemented an in vitro receptor-binding virus enrichment approach that recapitulates in vivo selection. Synthetic 6′-sialyl (N-acetyl-lactosamine) (6′ SLN) was used as the affinity ligand mimicking the human receptor to capture spontaneous viral receptor variants on the surface of magnetic beads. Starting with a pool of 108 EID50 of A/Vietnam/1203/2004 (VN04 virus), we performed four consecutive rounds of in vitro binding and elution followed by isolation of 150 individual virus clones by plaque purification and characterization by sequence analysis.
No “genetic engineering” here – or furore over “killer viruses escaping the lab!” Possibly because (a) “mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets”, and (b) “a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets” [my emphasis].
Meaning they didn’t actually make anything that could immediately elicit such scare-mongering as the more notorious studies I and many others have reported on previously.
However, the grim NSABB folk were quick to decry the publication, saying “”I think it is fair to say that we would have liked to have seen it before it was published,” [Paul Keim, chairman of the National Science Advisory Board for Biosecurity], and the “…altered bird flu virus could mutate in dangerous ways if unleashed in nature”.
I am more worried, to be perfectly honest, over the dangerous ways the the wild type virus could mutate IN nature, given that mutants can be selected so apparently easily!