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Dangerous for ferrets: lethal for humans?
Peter C Doherty1,2 and Paul G Thomas2
Corresponding authors: Peter C Doherty peter.doherty@stjude.org - Paul G Thomas paul.thomas@stjude.org
Author Affiliations
1 Department of Microbiology and Immunology, University of Melbourne, Vic 3010, Australia
2 Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
BMC Biology 2012, 10:10 doi:10.1186/1741-7007-10-10
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7007/10/10
Received: 15 February 2012
Accepted: 20 February 2012
Published: 20 February 2012
? 2012 Doherty and Thomas; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The influenza A viruses remain our most serious, known pandemic threat [1]. The possibility that a H5N1 high-pathogenicity avian influenza A virus (HPAI) could cross over to become established in humans has been a very real concern for more than a decade. As a consequence, it was big news at the recent Malta ESWI [2] meeting when Ron Fouchier from the Erasmus Medical Centre in Rotterdam announced that he had serially passaged an HPAI H5N1 virus in ferrets and achieved 'natural' ferret-to-ferret transmission. The first isolation ever (1933) of a human influenza A virus was in ferrets, and virologists generally regard these mustelids as the optimal model for most aspects of human influenza, including spread. It was not highlighted in Malta, but we learned later that Yoshi Kawaoka at the University of Wisconsin, Madison had similar findings, though he started with a virus that had been genetically modified in ways that might be expected to make it less virulent. It seems that others were also trying with reverse genetics approaches, but failed.
The Fouchier experiment was the talk of the Malta meeting, though not because of safety concerns. Influenza virologists had been debating for years whether these HPAI H5N1 viruses could ever change in a way that would allow them to transmit readily between human beings. Informed opinion was strongly divided. We all knew that, given exposure to what has been assumed to be a large virus dose from an infected bird, people can develop severe H5N1 disease, with a very high death rate (345 fatalities out of 584 cases since 2003) [3]. A few instances where family members may have been secondarily infected are on record, while two recent cases with no known history of avian contact have been reported from China. We are not there yet, but what these ferret adaptation studies suggest (though by no means prove) is that a 'human' H5N1 pandemic virus may indeed emerge from nature.
The issue of safety blew up much later when it came to publishing the Fouchier et al. findings. Should these genetic changes be 'out there' for all to see? Might that information be used by sophisticated bioterrorists? The furor about whether these ferret adaptation studies should ever have been done and, if so, whether the results should be openly published came as something of a surprise to us. Though some medical epidemiologists did raise the issue of risk, the resurrection of the catastrophic 1918 H1N1 virus by Jeff Taubengerger, Johan Hultin et al. more than a decade back met with general acclaim as an undoubted scientific achievement. The 1918 virus killed around 50 million people but nobody, so far as we recall, objected when (from 1999) segments of the virus sequence started to appear in the journals. Was the difference that there was, at that time, more trust in those who work in high security government laboratories? Then, much of the 1918 sequence was published before 9/11, 2001. The world has changed.
...
full article
http://www.biomedcentral.com/1741-7007/10/10
Peter C Doherty1,2 and Paul G Thomas2
Corresponding authors: Peter C Doherty peter.doherty@stjude.org - Paul G Thomas paul.thomas@stjude.org
Author Affiliations
1 Department of Microbiology and Immunology, University of Melbourne, Vic 3010, Australia
2 Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
BMC Biology 2012, 10:10 doi:10.1186/1741-7007-10-10
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7007/10/10
Received: 15 February 2012
Accepted: 20 February 2012
Published: 20 February 2012
? 2012 Doherty and Thomas; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The influenza A viruses remain our most serious, known pandemic threat [1]. The possibility that a H5N1 high-pathogenicity avian influenza A virus (HPAI) could cross over to become established in humans has been a very real concern for more than a decade. As a consequence, it was big news at the recent Malta ESWI [2] meeting when Ron Fouchier from the Erasmus Medical Centre in Rotterdam announced that he had serially passaged an HPAI H5N1 virus in ferrets and achieved 'natural' ferret-to-ferret transmission. The first isolation ever (1933) of a human influenza A virus was in ferrets, and virologists generally regard these mustelids as the optimal model for most aspects of human influenza, including spread. It was not highlighted in Malta, but we learned later that Yoshi Kawaoka at the University of Wisconsin, Madison had similar findings, though he started with a virus that had been genetically modified in ways that might be expected to make it less virulent. It seems that others were also trying with reverse genetics approaches, but failed.
The Fouchier experiment was the talk of the Malta meeting, though not because of safety concerns. Influenza virologists had been debating for years whether these HPAI H5N1 viruses could ever change in a way that would allow them to transmit readily between human beings. Informed opinion was strongly divided. We all knew that, given exposure to what has been assumed to be a large virus dose from an infected bird, people can develop severe H5N1 disease, with a very high death rate (345 fatalities out of 584 cases since 2003) [3]. A few instances where family members may have been secondarily infected are on record, while two recent cases with no known history of avian contact have been reported from China. We are not there yet, but what these ferret adaptation studies suggest (though by no means prove) is that a 'human' H5N1 pandemic virus may indeed emerge from nature.
The issue of safety blew up much later when it came to publishing the Fouchier et al. findings. Should these genetic changes be 'out there' for all to see? Might that information be used by sophisticated bioterrorists? The furor about whether these ferret adaptation studies should ever have been done and, if so, whether the results should be openly published came as something of a surprise to us. Though some medical epidemiologists did raise the issue of risk, the resurrection of the catastrophic 1918 H1N1 virus by Jeff Taubengerger, Johan Hultin et al. more than a decade back met with general acclaim as an undoubted scientific achievement. The 1918 virus killed around 50 million people but nobody, so far as we recall, objected when (from 1999) segments of the virus sequence started to appear in the journals. Was the difference that there was, at that time, more trust in those who work in high security government laboratories? Then, much of the 1918 sequence was published before 9/11, 2001. The world has changed.
...
full article
http://www.biomedcentral.com/1741-7007/10/10