virology blog
About viruses and viral disease
On episode #287 of the science show This Week in Virology, Matt Frieman updates the TWiV team on MERS-coronavirus, and joins in a discussion of whether we should further regulate research on potentially pandemic pathogens.
You can find TWiV #287 at www.microbe.tv/twiv.
From Martin Enserink at ScienceInsider:
Virologist Ron Fouchier has suffered a loss in a legal battle with the Dutch government over the publication of his controversial H5N1 influenza research. On Friday, a Dutch district court ruled that the government was right to ask Fouchier to obtain an export license before sending two hotly debated papers out for publication.
Readers of this blog will remember the furor sparked by Fouchier’s experiments in 2011 in which he developed an avian influenza H5N1 isolate that could transmit among ferrets by aerosol. When Fouchier was ready to publish the results, the Dutch government required that Fouchier apply for an export license. In so doing they were applying EU regulations that are designed to prevent the spread of biological weapons.
Fouchier applied for and was granted an export license on 27 April 2012. Fouchier’s employer, Erasmus Medical Center, appealed the decision to require an export license for this type of work. It is this appeal that was recently denied by a Dutch district court.
Fouchier rightfully claims that such EU regulations put him at a disadvantage compared with other groups. For example, Kawaoka’s findings on aerosol-transmitted avian influenza H5N1 virus in ferrets were not subject to EU export rules and were published ahead of Fouchier’s paper. I can understand Fouchier’s position; science is very competitive and being the first to publish is a coveted position. I am not sure that this is an issue worth bringing to the courts: even though Fouchier published after Kawaoka, most virologists credit the observations to both laboratories. The Dutch government should recognize that its scientists must be internationally competitive and expedite such future requests.
In my view, there is a larger issue at stake here: what constitutes research that requires an export license? I would argue that the avian influenza H5N1 virus that Fouchier produced is not a biological weapon. Remember that while this virus could transmit among caged ferrets by aerosol, it was markedly attenuated. In other words, gaining the ability to transmit by aerosol came at a fitness cost that reduced the virulence of the virus in ferrets. Such a virus is not a biological weapon, and should not have been subject to EU export requirements.
I do not know who in the Dutch government reviews such export license requests, but hopefully the next time Fouchier or any other virologist applies, there will be knowledgeable virologists involved in making the correct decision.
A group of virologists lead by Yoshihiro Kawaoka and Ron Fouchier have sent a letter to Nature and Science outlining the experiments they propose to carry out with influenza H7N9 virus.
Avian influenza H7N9 virus has caused over 130 human infections in China with 43 fatalities. The source of the virus is not known but is suspected to be wet market poultry. No human to human transmission have been detected, and the outbreak seems to be under control. According to the authors of the letter, the virus could re-emerge this winter, and therefore additional work is needed to assess the risk of human infection.
The research that the virologists propose involve gain-of-function experiments which provide the H7N9 virus with new properties. The isolation of avian influenza H5N1 viruses that can transmit by aerosol among ferrets is an example of a gain-of-function experiment.
The proposed gain-of-function experiments fall into five general categories:
I believe that the proposed gain-of-function experiments are all worth doing. I do not share the concerns of others about the potential dangers associated with gain-of-function experiments: for example the possibility that a virus selected for higher virulence could escape the laboratory and cause a lethal pandemic. Gain-of-function is almost always accompanied by a loss-of-function. For example, the H5N1 viruses that gained the ability to transmit by aerosol among ferrets lost their virulence by this route of infection. When these experiments are done under the proper containment, the likelihood that accidents will happen is extremely small.
All the proposed experiments that would use US funds will have to be reviewed and approved by the Department of Health and Human Services:
The HHS review will consider the acceptability of these experiments in light of potential scientific and public-health benefits as well as biosafety and biosecurity risks, and will identify any additional risk-mitigation measures needed.
While I understand that the authors wish to promote a dialogue on laboratory safety and dual-use research, I question the ultimate value of the communication. Because the letter has been published in two scientific journals, I assume that the target audience of the letter is the scientific community. However, the letter will clearly have coverage in the popular press and I am certain that it will be misunderstood by the general public. I can see the headlines now: “Scientists inform the public that they will continue to make deadly flu viruses”. The controversy about the H5N1 influenza virus transmission studies in ferrets all began with a discussion of the results before the scientific papers had been published. I wonder if the publication of these letters will spark another controversy about gain-of-function research.
In my view, science is best served by the traditional process known to be highly productive: a grant is written to secure funding for proposes experiments, the grant proposal is subject to scientific review by peers, and based on the review the work may or may not be supported. The experiments are done and the results are published. I do not understand why it is necessary to trigger outrage and debate by announcing the intent to do certain types of experiments.
I am curious to know what the many readers of virology blog – scientists and non-scientists – feel about the publication of this letter. Please use the comment field below to express your views on this topic.
On episode #241 of the science show This Week in Virology, Vincent, Alan, Rich and Kathy review how human placental trophoblasts confer viral resistance via exosome-mediated delivery of microRNAs, and isolation of the first human influenza virus in 1933.
You can find TWiV #241 at www.microbe.tv/twiv.
On epside #236 of the science show This Week in Virology, Vincent, Alan and Kathy review novel approaches to preventing influenza virus infection.
You can find TWiV #236 at www.microbe.tv/twiv.
There have been 131 confirmed human infections with avian influenza H7N9 virus in China, but so far there is little evidence for human to human transmission. Three out of four patients report exposure to animals, ‘mostly chickens‘, suggesting that most of the infections are zoonoses. Whether or not the virus will evolve to transmit among humans is anyone’s guess. Meanwhile it has been found that one of the H7N9 virus isolates from Shanghai can transmit by aerosol among ferrets, albeit inefficiently.
Ferrets were inoculated intranasally with influenza A/Shanghai/02/2013 virus or A/California/07/2009, the 2009 pandemic H1N1 virus. One to two days later the ferrets developed fever, sneezing, coughing, and nasal discharge; both viruses induced similar clinical signs. Virus was shed in nasal secretions for 7 days. Six infected ferrets were then divided among three separate cages, and each group was housed with a naive ferret, and a second uninfected animal was placed in an adjacent cage. Airflow was controlled so that air flowed from the cage of infected animals towards the cage of naive animals. Transmission of infection was measured by observing clinical signs, and measuring virus shedding in nasal secretions and hemagglutination-inhibition antibodies in serum.
Of the three ferrets housed in the same cage with H7N9 virius-infected animals, all three had signs of infection (sneeze, cough, nasal discharge), shed virus in nasal secretions, and developed anti-HA antibodies. All three ferrets in neighboring cages developed signs of infection, but only one shed virus in nasal secretions, and two of three seroconverted. From these data the authors conclude that H7N9 virus is ‘efficiently transmitted between ferrets by direct contact, but less efficiently by airborne exposure’. In contrast, transmission of H1N1 virus to naive ferrets by contact or aerosol was efficient (3/3 animals in both cases).
The authors also found that pigs could be infected intranasally with A/Shanghai/02/2013 virus: the animals shed virus in nasal secretions and developed clinical symptoms. However the infected pigs transmitted infection inefficiently to other pigs by contact or aerosol, or to ferrets by aerosol.
The  authors’ equivocal conclusion that “Under appropriate conditions human to human transmission of the H7N9 virus may be possible” could have been reached even before these experiments were done. Their results provide no information on whether the virus can undergo human to human transmission because animal models are not definitive predictors of what might occur in humans. I disagree with the authors’ statement on page 5, “Efficient transmission of influenza viruses in ferrets is considered as a predictor of human to human transmissibility’. While many influenza virus strains that transmit among humans by aerosol also do so in ferrets, this does not mean that human transmission of a novel virus can be predicted by animal experiments.
Infection of ferrets with A/Shanghai/02/2013 or or A/California/07/2009 virus results in mild disease with no mortality. In contrast, 32 humans infected with H7N9 virus have died, and many humans have died after H1N1 infection. These findings further emphasize the differences in influenza virus pathogenesis in ferrets and humans.