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.

To keep up with the large body of data from H5N1 GOF publications, the Centers for Disease Control and Prevention (CDC) in collaboration with domestic and international researchers compiled published amino acid mutations and protein motifs that were tested experimentally and shown to alter relevant functional aspects of H5N1 virus phenotypes in the H5N1 Genetic Changes Inventory (38) . While this type of data had been used at CDC for many years to conduct molecularly based surveillance of naturally occurring influenza viruses, the end result of the H5N1 Genetic Changes Inventory was to provide a single point of reference to facilitate the efficient identification of specific mutations or motifs in viral proteins that might signal adaptation to mammalian species, changes in susceptibility to antiviral medications, or changes in viral pathogenesis and transmissibility. By focusing on mutations specifically identified as conferring GOF phenotypes, veterinary and public health experts have used the Genetic Changes Inventory to help assess the relevance of molecular markers identified in naturally occurring viruses. During pandemic risk assessment, viral sequence data are weighed with respect to other virologic and epidemiological traits of a newly identified virus.