Advertisement

Bird Flu Transmission in Mammals

After much ado, Nature publishes the first report of a bird flu virus adapted for transmission in ferrets.

By | May 2, 2012

image: Bird Flu Transmission in Mammals

A long-anticipated paper detailing the creation of an artificial strain of H5N1 bird flu virus that, while less lethal, is capable of transmission in mammals has been published today (May 2) in Nature. The report reveals that a real-world conversion of H5N1 to a form that could cause a pandemic in humans is potentially only a few mutations away.

“[The study] has disproven the tenet held by some influenza virologists that this particular high-pathology avian flu could not adapt to transmission in mammals,” said Stan Lemon of the University of North Carolina, who was not involved in the research. “Now we know that that can happen it is a bit of a wake-up call.”

Some scientists had doubted the possibility that H5N1 bird flu could adapt to human transmission, Lemon explained, because “influenza viruses are primarily viruses of birds… and previous human epidemics or pandemics have always had an H3 or an H1 hemagglutinin”—the protein that recognizes receptors on the surfaces of cells and allows the virus to enter. “There’s never been an H5 hemagglutinin gene in a virus that has been rapidly and efficiently transmitted between mammals,” he said.

And it might not take much to convert the H5 protein, noted senior author Yoshihiro Kawaoka of the University of Wisconsin, Madison in an email to The Scientist. “Only a few mutations are needed to confer transmissibility [in mammals],” he said. “This will make it important to stockpile vaccine and antivirals and optimize pandemic preparedness measures.”

Of course, this publication is not the first time the scientific community has heard about these results. Indeed, Kawaoka’s study, along with a similar study led by Ron Fouchier at the Erasmus Medical Center in Rotterdam, the Netherlands (which is pending publication at Science), has been making headlines since late last year, when the National Science Advisory Board for Biosecurity (NSABB) made the unprecedented move of recommending that certain details be redacted prior to publication, for fear that they could be used for wrongdoing. But after further discussion, both the NSABB and the World Health Organization (WHO) decided that it was in the best interest of science to publish both papers in full.

The publication does lay to rest some questions regarding the details of the study, such as the fact that the engineered virus is not as lethal as the naturally existing strains of H5N1, which have killed about half of the people they have infected. This is because Kawaoka and colleagues paired mutant H5 proteins, which conferred transmissibility among the ferrets, with virus particles from a much less deadly H1N1 virus, creating what are known as reassortant viruses. “This approach enabled us to focus on the role of the H5N1 virus hemagglutinin without the complex background of the other genes,” explained Kawaoka.

Randomly mutating the H5 gene, the researchers found two mutations that, in combination, allowed the viruses to bind to the mammal-specific receptors in vitro. They then tested the reassortant viruses in vivo, by putting the viruses up ferrets’ noses and caging these infected ferrets next to non-infected ferrets, which contracted the virus in a matter of days. During the infections, two additional mutations arose in H5 that conferred improved growth and transmission of the virus. But thanks to the less virulent H1N1 components, no ferrets died.

Despite the fact that the researchers are working with a combination of viruses, the study does have real-world significance, said Kawaoka. “Many influenza genomes are capable of reassorting to generate hybrid viruses if they infect one host.”

The team’s findings could both inform the development of vaccines and aid in the monitoring of circulating viruses for signs that they are acquiring mutations conferring transmission between mammals. “If surveillance teams know which mutations are important," Kawaoka said, "they can be alert for the emergence of viruses with pandemic potential.”

In their attempt to prepare for such deadly outbreaks, however, the researchers might have created an alternative worst-case scenario, argued Richard Ebright of Rutgers University, New Jersey. “The research has benefits in terms of expanding our fundamental understanding of influenza evolution and biology, and some potential practical applications in terms of surveillance and response, but these benefits do not match, much less outweigh, the risks,” he said, which include not just bioterrorism, but accidental escape of the virus or deliberate release by a disgruntled or disturbed lab worker. (Read more about Ebright’s thoughts on the risks of such research in last month’s feature, “Deliberating Over Danger.”)

“On the other hand, there is a very definite risk, and I think of greater magnitude, that this virus will evolve in nature,” said Lemon. “Four mutations is not a lot, [especially considering that] RNA viruses are highly mutable—the kinds of viruses that very readily adapt to new environments…. We need to be ready to observe that happening, predict it happening, and counteract it. From my own perspective, the risks of nature being a terrorist here are much greater than the risks of some misguided scientist.”

M. Imai et al., “Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets,” Nature, doi:10.1038, 2012.

Advertisement

Add a Comment

Avatar of: You

You

Processing...
Processing...

Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Comments

Avatar of: edo_mcgowan

edo_mcgowan

Posts: 19

May 3, 2012

Assume a mild outbreak that can be confined to a single community and
that community is highly quarantined. This is what was done with SARS in
Toronto. But, forgotten by all were routes out of the quarantined
areas, namely the sewers. Sewer plants, we must remember, are major
aerosol generators, that is a documented fact. Thus some questions that
warrant consideration here would include: 1) do sewer plants kill all
organisms that enter them---the answer is that they actually do a fairly
poor job and that also has been documented. 2) even before the raw
sewage gets to a disinfection stage within the sewer plant, which is
usually at the tail end of the process, it is subjected to high rates of
aeration, hence aerosol generation. These issues need serious consideration and thus contingency plans.

Dr Edo McGowan, Medical Geo-hydrology

Avatar of: Edward R. Mikol

Edward R. Mikol

Posts: 1457

May 3, 2012

Unless they produced an antidote with this research, publishing the findings is folly.

Calling Nature a "terrorist" -to deflect from the historically-common, malignant human project of mass-murder for ideological reasons - is cute, but irrelevant.

Use the investigations to solve the threat, and keep the intermediate work under wraps to prevent conscious terrorists (Nature is not consciously intent on producing this pandemic while many human agents would be) from benefiting from "pure" scientists who appear unable to appreciate the reality of human destructiveness.

Avatar of:

Posts: 0

May 3, 2012

Assume a mild outbreak that can be confined to a single community and
that community is highly quarantined. This is what was done with SARS in
Toronto. But, forgotten by all were routes out of the quarantined
areas, namely the sewers. Sewer plants, we must remember, are major
aerosol generators, that is a documented fact. Thus some questions that
warrant consideration here would include: 1) do sewer plants kill all
organisms that enter them---the answer is that they actually do a fairly
poor job and that also has been documented. 2) even before the raw
sewage gets to a disinfection stage within the sewer plant, which is
usually at the tail end of the process, it is subjected to high rates of
aeration, hence aerosol generation. These issues need serious consideration and thus contingency plans.

Dr Edo McGowan, Medical Geo-hydrology

Avatar of:

Posts: 0

May 3, 2012

Unless they produced an antidote with this research, publishing the findings is folly.

Calling Nature a "terrorist" -to deflect from the historically-common, malignant human project of mass-murder for ideological reasons - is cute, but irrelevant.

Use the investigations to solve the threat, and keep the intermediate work under wraps to prevent conscious terrorists (Nature is not consciously intent on producing this pandemic while many human agents would be) from benefiting from "pure" scientists who appear unable to appreciate the reality of human destructiveness.

Avatar of:

Posts: 0

May 4, 2012

I am once again astounded at the naivety of scientific researchers who will open Pandora's box in the name of discovery and then seek to publish without any regard to the very real psychology of the human masses, some of which will gladly exploit any potential weapon to unleash on their particular enemies.  It is beyond myopic to assume that people who would engage in terroristic acts, whether small splinter groups, rougue nations, disturbed individuals or even people employed at high levels in otherwise responsible governments, will fail to exploit this method of forced mutation of what is acknowledged to be a dangerous virus.

Once again we have a living example of people so smart in their field that they are stupid in all other areas.  The US government's attempt to sequester this story was entirely appropriate, for the good of humanity around the world.

Avatar of:

Posts: 0

May 4, 2012

Dad_ I'm astounded at the naiety of your comments/assessments and those of others.  Biological warfare programs have been pursued, and USED, by governments dating back to the early 1900s (see Ken Alibek's Biohazard) at least.  This isn't giving anyone a new idea, and terrorists have far deadlier agents at their disposal that are far easier to obtain and weaponize at this moment without genetic alteration or work of any kind.  There are no government stocks of H5N1 or H1N1, but there are stockpiles of vaccines and treatments.  Contrast that against smallpox where we neither routinely make or store more vaccine than is necessary for the military because it has been "erradicated", despite stores of the virus in the US and Russia, and Russia's known proclivity to be laissez faire with its management.

Disseminating information of this type to the scientific community allows those with access to the proper facilities and funding to advance the search for vaccines and treatments much faster than a terrorist group potentially pursuing a nefarious use of the same research.  I work in a viral lab.  If we wanted to repeat these researchers' work, we couldn't.  The obstacles to a terrorist group doing it, and producing it en masse, is just not a reasonable conclusion based on rationale thought.

Avatar of: Dad_Fourkids

Dad_Fourkids

Posts: 6

May 4, 2012

I am once again astounded at the naivety of scientific researchers who will open Pandora's box in the name of discovery and then seek to publish without any regard to the very real psychology of the human masses, some of which will gladly exploit any potential weapon to unleash on their particular enemies.  It is beyond myopic to assume that people who would engage in terroristic acts, whether small splinter groups, rougue nations, disturbed individuals or even people employed at high levels in otherwise responsible governments, will fail to exploit this method of forced mutation of what is acknowledged to be a dangerous virus.

Once again we have a living example of people so smart in their field that they are stupid in all other areas.  The US government's attempt to sequester this story was entirely appropriate, for the good of humanity around the world.

Avatar of: oussu

oussu

Posts: 7

May 4, 2012

Dad_ I'm astounded at the naiety of your comments/assessments and those of others.  Biological warfare programs have been pursued, and USED, by governments dating back to the early 1900s (see Ken Alibek's Biohazard) at least.  This isn't giving anyone a new idea, and terrorists have far deadlier agents at their disposal that are far easier to obtain and weaponize at this moment without genetic alteration or work of any kind.  There are no government stocks of H5N1 or H1N1, but there are stockpiles of vaccines and treatments.  Contrast that against smallpox where we neither routinely make or store more vaccine than is necessary for the military because it has been "erradicated", despite stores of the virus in the US and Russia, and Russia's known proclivity to be laissez faire with its management.

Disseminating information of this type to the scientific community allows those with access to the proper facilities and funding to advance the search for vaccines and treatments much faster than a terrorist group potentially pursuing a nefarious use of the same research.  I work in a viral lab.  If we wanted to repeat these researchers' work, we couldn't.  The obstacles to a terrorist group doing it, and producing it en masse, is just not a reasonable conclusion based on rationale thought.

Avatar of: therealistt

therealistt

Posts: 1

May 5, 2012

Agreed. Also to make a simple point, look at the numbers. The chances of a terrorist group choosing to weaponize this specific strain as opposed to the number of significantly easier strains are slim. In the event that this occurs, there would be an exponential amount of "good" scientists trying to create a vaccine for it, who already had a lot of groundwork provided for them.

Avatar of:

Posts: 0

May 5, 2012

Agreed. Also to make a simple point, look at the numbers. The chances of a terrorist group choosing to weaponize this specific strain as opposed to the number of significantly easier strains are slim. In the event that this occurs, there would be an exponential amount of "good" scientists trying to create a vaccine for it, who already had a lot of groundwork provided for them.

Avatar of:

Posts: 0

May 19, 2012

You know I can understand this happening in the main stream media, but a scientific publication should due able to get the correct sort of ferret as a main illustration. You show the North American Black Footed Ferret (Mustela nigripes), which is a wild animal and an endangered species. Indeed it is in no way an appropriate lab animal. Instead you should have shown a picture of the typical domesticated ferret (Mustela putorius euro), which was used in the study, and is a good lab model for respiratory diseases.

Avatar of: Larry Lyons

Larry Lyons

Posts: 1

May 19, 2012

You know I can understand this happening in the main stream media, but a scientific publication should due able to get the correct sort of ferret as a main illustration. You show the North American Black Footed Ferret (Mustela nigripes), which is a wild animal and an endangered species. Indeed it is in no way an appropriate lab animal. Instead you should have shown a picture of the typical domesticated ferret (Mustela putorius euro), which was used in the study, and is a good lab model for respiratory diseases.

Avatar of: dfedson

dfedson

Posts: 2

May 21, 2012

The debate over restricting publication
of the experimental details of the H5N1 research by Fouchier and Kawaoka misses
a larger point. Influenza viruses can and do develop more efficient
transmissibility on their own; we've known this for decades. What's more
important is to understand what we might do to reduce mortality when this
happens. Immunomodulatory agents could probably be used to modify the host
response to severe influenza and improve survival (Influenza Other Respi Virus
2009; 3: 129-42). Evidence that this happens was published recently. In a study
of patients hospitalized with laboratory-confirmed influenza, statin treatment
reduced mortality by 41% (J Infect Dis 2012; 205: 13-9). The reduction in
mortality was in addition to any benefit that might have been due to previous
influenza vaccination or antiviral treatment. Influenza scientists and the
public health officials who listen to them have yet to understand the potential
importance of these agents, yet if a highly virulent H5N1 virus gets loose, the
vaccines and antivirals they're counting on won't be available in time to do
much good. The issue we should be discussing is not whether to undertake or
publish research on H5N1 influenza virus transmission; it's why we have failed
to undertake laboratory and clinical research on immunomodulatory agents that
could save lives. These agents are produced as generics in developing countries
and could be used to treat anyone with access to basic health care. The cost of
treating an individual patient would be less than one dollar.

 

Avatar of:

Posts: 0

May 21, 2012

The debate over restricting publication
of the experimental details of the H5N1 research by Fouchier and Kawaoka misses
a larger point. Influenza viruses can and do develop more efficient
transmissibility on their own; we've known this for decades. What's more
important is to understand what we might do to reduce mortality when this
happens. Immunomodulatory agents could probably be used to modify the host
response to severe influenza and improve survival (Influenza Other Respi Virus
2009; 3: 129-42). Evidence that this happens was published recently. In a study
of patients hospitalized with laboratory-confirmed influenza, statin treatment
reduced mortality by 41% (J Infect Dis 2012; 205: 13-9). The reduction in
mortality was in addition to any benefit that might have been due to previous
influenza vaccination or antiviral treatment. Influenza scientists and the
public health officials who listen to them have yet to understand the potential
importance of these agents, yet if a highly virulent H5N1 virus gets loose, the
vaccines and antivirals they're counting on won't be available in time to do
much good. The issue we should be discussing is not whether to undertake or
publish research on H5N1 influenza virus transmission; it's why we have failed
to undertake laboratory and clinical research on immunomodulatory agents that
could save lives. These agents are produced as generics in developing countries
and could be used to treat anyone with access to basic health care. The cost of
treating an individual patient would be less than one dollar.

 

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube
Advertisement
Ingenuity
Ingenuity

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
CEM
CEM
Advertisement
NeuroScientistNews
NeuroScientistNews
Life Technologies