May 2, 2012

expert reaction to adaptation of an influenza virus

After months of controversy over two research papers which showed how the H5N1 flu virus could be mutated to become transmissible in humans, Nature published the first of the papers following a reversal of NSABB’s decision to restrict publication.

Dr John McCauley, Director of the WHO Collaborating Centre for Influenza at the MRC National Institute for Medical Research, said:

“While we understand the concerns raised about the publication of this research, we are very pleased that it is now available. The Medical Research Council’s policy on Bioterrorism and Medical Research clearly outlines the considerations which have to be made when making funding decisions about work of this nature. The study published in Nature is an important piece of the puzzle at the WHO Collaborating Centre for Influenza at the MRC National Institute for Medical Research, who are trying to put together a clearer picture of how these viruses might spread from human to human and understand the evolution of these viruses that have proved so devastating for birds and could yet do so for humans.””

The policy can be found here

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

“This is a significant piece of research. The work is elegantly performed and contributes new knowledge in two ways:

“First it describes the use of randomly generating influenza mutants in the lab and phenotypically selecting them, in a way that speeds up what nature is doing. This allowed the identification of novel mutations that altered the H5 HA receptor binding specificity.

“However, what is interesting is that although this approach was good enough to pull out the receptor binding changes it was designed to find, it did not in the end solve the mystery of transmissibility because there is more to it than that: in other words we are always limited by our lack of knowledge when designing the best screens.

“In the end the approach gave the helping hand that allowed the virus to replicate well enough in the right place in the ferret to then select, by a more traditional forward genetic approach, mutations that affect the stability of the HA protein. This is a new finding.

“The second piece of novel information in the paper is that HA needs to be stable to be transmissible through the air between mammals. With hindsight it makes perfect sense that the virus has to be very stable to survive in acidic conditions whilst it is outside the cell, others have also pointed out before that the nose can be a relatively acidic environment.

“I think what we can conclude concerning surveillance efforts is that sequencing on its own might never be enough – the virus can make changes in amino acids of HA (and probably other genes) that affect transmissibility in ways that we might not have previously imagined.

“We know now more about how an avian virus has to change to become transmissible, but we need to bear in mind that the mutations we pick up during surveillance in the wild need to not only be mapped onto the three-dimensional structure of the HA protein, but also understood in terms of their effects on behaviour of the virus in order to know if they are to be taken seriously.”

‘Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets’ by Imai et al., published in Nature on Wednesday 2nd May.