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.

Some GOF research resumed following the end of a voluntary global moratorium (36) . However, a new moratorium on funding certain types of GOF research on influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) viruses is now in place in the United States (37) . This pause provided an opportune time to describe how the molecular markers identified by the controversial ferret transmission studies and many other GOF studies have provided important information for public health risk assessment of naturally occurring viruses detected in animals and humans. Here we outline how we utilize a molecularly based surveillance approach focused on knowledge and insights gained from GOF research to inform influenza pandemic risk assessment, as well as risk management and pandemic preparedness. We present the dramatic increase in the number of human cases caused by HPAI H5N1 in Cambodia and an outbreak of influenza A(H7N9) in China during 2013 as examples of how the results of GOF studies supported a more rapid and accurate risk assessment and response to these situations. In both instances, molecularly based surveillance identified naturally occurring mutations in avian influenza viruses isolated from humans that had been demonstrated by GOF studies to increase transmissibility in the ferret model, prompting the public health actions described below.