Airborne transmission of H5N1 in ferrets – the Fouchier study

Two studies have recently been published demonstrating that H5N1 can be transmitted in the air in ferrets, one by Dr. Kawaoka’s group, the other by Dr. Fouchier’s group. I have previously discussed the Kawaoka paper. Here, I present some of the findings from the Fouchier paper.

Using their knowledge of influenza biology, these investigators modified the A/Indonesia/5/2005 strain of H5N1 to create three mutations which they believed would increase the odds of airborne spread of the virus – E627K in PB2 and Q222L and G224S in HA. They found that these three mutations were insufficient for this purpose. To create a selective pressure for ferret to ferret spread of the virus, the wild type and the genetically modified versions of H5N1 were used to infect two separate groups of ferrets and then passaged from ferret to ferret by collecting the sneezes of the infected ferrets and using these sneezes to infect additional ferrets. After 10 such passages from ferret to ferret, the genetically modifed, but not the wild type strain of H5N1, was able to infect ferrets through the air. Two additional mutations appeared to be under selection during the passaging process - T156A and H103Y in HA.

One of the ferrets died during the study, but apparently not due to infection through the air. Because the airborne strain had only been passaged 10 times, we do not know what would have happened after many more passages in mammals, as would occur in a pandemic. It is not unreasonable to suppose that the virus would have continued to adapt to mammals under these conditions. And we know that H5N1 which is fully adapted to birds is 100% lethal in some species.

How do the investigators who conducted these studies now view the odds that we will experience a H5N1 pandemic? From the paper:

Given the large numbers of HPAI A/H5N1 virus-infected hosts globally, the high viral mutation rate, and the apparent lack of detrimental effects on fitness of the mutations that confer airborne transmission, it may simply be a matter of chance and time before a human-to-human transmissible A/H5N1 virus emerges.

Airborne transmission of influenza A/H5N1 between ferrets. 2012. Herfst et al. Science. 336: 1534 – 1541.

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