June 21, 2012

expert reaction to publication of H5N1 papers

The publication of two papers on the mutation of the H5N1 flu virus in ferrets, one in Science and one in Nature, have been the cause of some controversy after a US government advisory board asked the two journals to delay publication. On the eventual publication of the Science paper, the SMC sent out quotes, having previously held a briefing and reacted to various developments in the story (here, here and here).

Professor Wendy Barclay, Chair in Influenza Virology, Imperial College London, said:

“We already had a pretty good idea that this paper was going to describe some mutations in the H5N1 HPAI that conferred transmissibility in ferrets. We also already suspected that some of these would affect receptor binding, switching the specificity of HA from a2,3sialic acid to a2,6. The real unknown here was the identity of the 4th HA mutation that is common to all the transmissible viruses in the Dutch study. We now know that this amino acid change is not exactly the same one as seem in the paper from Kawaoka’s group, but it sits in the same area of the HA protein, at the trimer interface. We might speculate therefore that the effect of this mutation is to alter the stability of the HA protein, as was shown mechanistically in the other paper. If that is the case, then we now have a much more robust biological basis to design screens that pick up this type of change and this will help us to detect when an avian virus turns the corner to become transmissible in humans.

“Not all of the mutations necessary for transmission in the ferret passage experiment have been previously found in nature. The two changes that affected receptor binding (Q222L G224S) have not been seen and although the group argue that other mutations that affect this trait have been found in viruses in the field, they also show in this paper that some of those changes (N182K) are not in fact sufficient to confer transmission. How much of a fitness cost these changes confer individually or when combined and in which species, will be important to establish before we can really assess how close we are to the H5 pandemic.

“This likelihood is modelled in the accompanying paper from Smith et al., but as always the modelling may be limited by the accuracy of available biological data. Hopefully more work from the biologists to help the mathematicians address how mutant influenza viruses with new properties evolve within a host will increase our ability to estimate the risks of pandemics as well as of antiviral resistance or the emergence of viruses with enhanced pathogenicity.”

‘Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets’ by Fouchier et al. and ‘The Potential for Respiratory Droplet–Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host’ by Smith et al., published in Science on Thursday 21st June.