Spatio-temporal dynamics of the evolution and spread of influenza A/H1N1pdm09 virus.

Human influenza A viruses impose a heavy burden on global public health. The latest human influenza pandemic virus (A/H1N1pdm09) that emerged in Mexico was devastating, resulting in more than 60 million cases and 12,469 deaths in the US. New antigenic variants with pandemic potential can constantly emerge via two different ways; 1) the accumulation of genetic mutations – antigenic drift, or 2) the exchange of genetic materials between two or more different viral subtypes to form new hybrid strains – antigenic shift. Such genetic changes of influenza A viruses may occur by chance, but it is population and environmental landscapes that drive such evolutionary processes of the virus and determine their geographic patterns of distribution and viral dissemination. Publicly available genetic sequence samples of the A/H1N1pdm09 virus with geographic sampling locations allow for the identification of how the landscape factors play differently on the evolution and spread of the viruses across different geographic scales. This work examines the geographic patterns of the evolution and spread of A/H1N1pdm09 virus as a result of the dynamic interaction between humans and the viruses at macro, meso, and micro scales using the methods and tools of disease ecology, landscape genetics, and phylogenetics. At a macro scale, after the emergence of the A/H1N1pdm09 virus in North America in 2009, the virus migrated to Asian countries via East Asia, and was then locally sustained in South Asia and the Malay Peninsula over the summer in temperate regions in the Northern Hemisphere. Geographic patterns of local persistence of the virus and the distribution of the viruses carrying amino acid substitutions indicated that South Asia was the major region where antigenic drift most likely occurred. At a meso scale, the results from phylogeographic analyses and network modeling indicated that the migration of the A/H1N1pdm09 virus in the United States was mediated by relative humidity in summer and winter, precipitation in winter, and urban population density and the size of urban populations, while geographic distance between states was not associated with viral transmission during the active phase of the pandemic. At micro scales in China, the isolation by distance patterns of the A/H1N1pdm09 virus indicated the negative correlation between geographic and genetic distance, implying that the local circulation was the main driver in the formation of the spatial genetic structure of the virus. These findings indicate that the population, cultural, and environmental landscapes played a significant role in the evolution and spread of the A/H1N1pdm09 virus across macro, meso, and micro scales. Better understanding of the evolutionary processes and spatial transmission of influenza A will allow us to develop effective surveillance and intervention strategies for future pandemics.