Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness

Davis, C. Todd; Chen, Li-Mei; Pappas, Claudia; Stevens, James; Tumpey, Terrence M.; Gubareva, Larisa V.; Katz, Jacqueline M.; Villanueva, Julie M.; Donis, Ruben O.; Cox, Nancy J.

Reverse-genetics experiments using the well-established ferret model to measure H5N1 respiratory droplet-mediated transmission were, until recently, unable to identify specific mutations involved in this process because the laboratory-derived viruses, like their wild-type counterparts, demonstrated a lack of or limited capacity for aerosol transmission (18, 19, 28) . However, studies from 2012 by Herfst et al. (29) and Imai et al. (21) were able to demonstrate that genetically modified H5N1 viruses could be transmitted relatively efficiently via respiratory droplets in a mammalian host following acquisition of specific mutations in the hemagglutinin (HA) and/or in combination with the presence of lysine at position 627 in the PB2 protein sequence. The controversy sparked by these studies continues to reverberate (21, 29) . Some have argued that benefits associated with H5N1 GOF transmission studies outweigh the risks (30-32), while others have stated that public health derived little to no benefit to justify the research (33) (34) (35) .