Circulating Avian Influenza viruses closely rlated to the 1918 virus Have pandemic potential

​A recent article by Watanabe et al. in the Cell Host & Microbe journal describes an attempt to assess the risk of emergence of pandemic influenza viruses closely related to the 1918 influenza virus.

Reverse genetics methods were used to generate an avian influenza virus closely related to the 1918 influenza virus, based on sequence information reported from various avian influenza viruses. Further experiments were done to demonstrate what mutations are required for this virus to become easily transmissible between mammals. Effectiveness of the current influenza vaccine and the antiviral drug oseltamivir against the 1918-like influenza virus was also assessed.

It was experimentally demonstrated that a 1918-like avian influenza virus with a limited number of additional mutations exhibits relatively high pathogenicity in mammals, although lower than the original 1918 influenza virus strain that was also recreated with reverse genetics technology in the laboratory. In the transmissibility studies, only some constellations of the virus genes allowed transmissibility between ferrets, suggesting roles for RNA replication complex, HA and NA in virus transmission.

To further assess the risk of the emergence of such avian influenza viruses that could infect humans, the team examined the prevalence of avian influenza viruses that are similar to the 1918 influenza virus, and looked for avian influenza viruses possessing human-type amino acid residues.

The study thus demonstrated the continued circulation of such avian influenza viruses that possess 1918 virus-like proteins and viruses that may acquire 1918 virus-like properties. This would suggest that a potential exists for a 1918-like pandemic virus to emerge from the avian virus gene pool.

ECDC comment

The study by Watanabe et al. is the latest in a series of genetic engineering experiments where research groups have created influenza viruses of pandemic potential. The new study discussed here further confirms the power of recombinant technology to create pathogenic viruses that are not currently circulating in nature. From the public health perspective, this poses a risk both for the laboratory personnel working with these viruses, even in very secure biosafety conditions, and to the general public in case of a laboratory escape. Recent incidents remind us that laboratory accidents and laboratory escapes can happen with dangerous pathogens, even if the highest security standards are applied [1,2,3]. The developments in technology should not and cannot be stopped and research laboratories should have the freedom to apply the latest technologies for science purposes as long as this is done with full adherence to good ethical and biosafety practices. However, the decision to fund this type of gain of pathogenic function studies in influenza viruses and other human pathogens has stirred scientific controversy about the mechanisms currently in place to ensure sound assessment of risk and benefits by independent reviewers [4].

The public health perspective to the critical review of funding such dual-use research of concern including studies aiming at the creation of potential pandemic pathogens has been so far limited. Very often the research groups justify their research agenda with pandemic preparedness and better understanding of the avian influenza viruses without further specifying how exactly the results may improve the preparedness plans. It is important to ask what this type of result adds to the field of pandemic influenza preparedness and how the prediction of efficacy of influenza vaccines or antivirals against influenza viruses is improved based on these results. Furthermore, it is pertinent to ask for justification of the methods, and if any of those could be replaced by safer experiments. It is of utmost importance that the biosafety practices and controls in the laboratories undertaking such research are kept to a high standard. A forum for public health discussion around dual-use research of concern topics is not yet available at European level. ECDC advocates for open discussion about studies where potential pandemic threats are created. The research community should in all their work apply the medical ethical principle of “first do no harm”.