Influenza A Virus Migration and Persistence in North American Wild Birds

Justin Bahl, Scott Krauss, Denise Kühnert, Mathieu Fourment, Garnet Raven, S Paul Pryor, Lawrence J Niles, Angela Danner, David Walker, Ian H Mendenhall, Yvonne CF Su, Vivien G Dugan, Rebecca A Halpin, Timothy B Stockwell, Richard J Webby, David E Wentworth, Alexei J Drummond, Gavin JD Smith, Robert G Webster

Abstract
Wild birds have been implicated in the emergence of human and livestock influenza. The successful prediction of viral spread and disease emergence, as well as formulation of preparedness plans have been hampered by a critical lack of knowledge of viral movements between different host populations. The patterns of viral spread and subsequent risk posed by wild bird viruses therefore remain unpredictable. Here we analyze genomic data, including 287 newly sequenced avian influenza A virus (AIV) samples isolated over a 34-year period of continuous systematic surveillance of North American migratory birds. We use a Bayesian statistical framework to test hypotheses of viral migration, population structure and patterns of genetic reassortment. Our results reveal that despite the high prevalence of Charadriiformes infected in Delaware Bay this host population does not appear to significantly contribute to the North American AIV diversity sampled in Anseriformes. In contrast, influenza viruses sampled from Anseriformes in Alberta are representative of the AIV diversity circulating in North American Anseriformes. While AIV may be restricted to specific migratory flyways over short time frames, our large-scale analysis showed that the long-term persistence of AIV was independent of bird flyways with migration between populations throughout North America. Analysis of long-term surveillance data provides vital insights to develop appropriately informed predictive models critical for pandemic preparedness and livestock protection.

Influenza A Virus Migration and Persistence in North American Wild Birds PLoS Pathogens (2013)

Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans

Justin Bahl, Martha I. Nelson, Kwok H. Chan, Rubing Chen, Dhanasekaran Vijaykrishna, Rebecca A. Halpin, Timothy B. Stockwell, Xudong Lin, David E. Wentworth, Elodie Ghedin, Yi Guan, J. S. Malik Peiris, Steven Riley, Andrew Rambaut, Edward C. Holmes, and Gavin J. D. Smith

Abstract

Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.

Proceedings of the National Academy of Sciences, in press

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Long-term evolution and transmission dynamics of swine influenza A virus

Dhanasekaran Vijaykrishna, Gavin J. D. Smith, Oliver G. Pybus, Huachen Zhu, Samir Bhatt, Leo L. M. Poon, Steven Riley, Justin Bahl, Siu K. Ma, Chung L. Cheung, Ranawaka A. P. M. Perera, Honglin Chen, Kennedy F. Shortridge, Richard J. Webby, Robert G. Webster, Yi Guan & J. S. Malik Peiris

Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12 years of systematic surveillance in this region, supplemented with data stretching back 34 years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.

Nature 473, 519–522; doi:10.1038/nature10004

Ancient origins determine global biogeography of hot and cold desert cyanobacteria

Justin Bahl, Maggie C. Y. Lau, Gavin J. D. Smith, Dhanasekaran Vijaykrishna, S. Craig Cary, Donnabella C. Lacap, Charles K. Lee, R. Thane Papke, Kimberley A. Warren-Rhodes, Fiona K. Y. Wong, Christopher P. McKay & Stephen B. Pointing

Factors governing large-scale spatio-temporal distribution of microorganisms remain unresolved, yet are pivotal to understanding ecosystem value and function. Molecular genetic analyses have focused on the influence of niche and neutral processes in determining spatial patterns without considering the temporal scale. Here, we use temporal phylogenetic analysis calibrated using microfossil data for a globally sampled desert cyanobacterium, Chroococcidiopsis, to investigate spatio-temporal patterns in microbial biogeography and evolution. Multilocus phylogenetic associations were dependent on contemporary climate with no evidence for distance-related patterns. Massively parallel pyrosequencing of environmental samples confirmed that Chroococcidiopsis variants were specific to either hot or cold deserts. Temporally scaled phylogenetic analyses showed no evidence of recent inter-regional gene flow, indicating populations have not shared common ancestry since before the formation of modern continents. These results indicate that global distribution of desert cyanobacteria has not resulted from widespread contemporary dispersal but is an ancient evolutionary legacy. This highlights the importance of considering temporal scales in microbial biogeography.

Nature Communications 2, Article number: 163 doi:10.1038/ncomms1167

Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development

Mariette F. Ducatez, Justin Bahl, Yolanda Griffin, Evelyn Stigger-Rosser, John Franks, Subrata Barman, Dhanasekaran Vijaykrishna, Ashley Webb, Yi Guan, Robert G. Webster, Gavin J. D. Smith, and Richard J. Webby

Since the reemergence of highly pathogenic H5N1 influenza viruses in humans in 2003, these viruses have spread throughout avian species in Asia, Europe, and Africa. Their sustained circulation has resulted in the evolution of phylogenetically diverse lineages. Viruses from these lineages show considerable antigenic variation, which has confounded vaccine planning efforts. We reconstructed ancestral protein sequences at several nodes of the hemagglutinin (HA) and neuraminidase (NA) gene phylogenies that represent ancestors to diverse H5N1 virus clades. By using the same methods that have been used to generate currently licensed inactivated H5N1 vaccines, we were able to produce a panel of replication competent influenza viruses containing synthesized HA and NA genes representing the reconstructed ancestral proteins. We identified two of these viruses that showed promising in vitro cross-reactivity with clade 1, 2.1, 2.2, 2.3.4, and 4 viruses. To confirm that vaccine antigens derived from these viruses were able to elicit functional antibodies following immunization, we created whole-virus vaccines and compared their protective efficacy versus that of antigens from positive control, naturally occurring, and broadly reactive H5N1 viruses. The ancestral viruses’ vaccines provided robust protection against morbidity and mortality in ferrets challenged with H5N1 strains from clades 1, 2.1, and 2.2 in a manner similar to those based on the control strains. These findings provide proof of principle that viable, computationally derived vaccine seed viruses can be constructed within the context of currently licensed vaccine platforms. Such technologies should be explored to enhance the cross reactivity and availability of H5N1 influenza vaccines.

Proceedings of the National Academy of Sciences 108: 349–354.