Author
Aeron C. Hurt
Other affiliations: World Health Organization, University of Melbourne, Federation University Australia ...read more
Bio: Aeron C. Hurt is an academic researcher from Hoffmann-La Roche. The author has contributed to research in topics: Influenza A virus & Neuraminidase. The author has an hindex of 49, co-authored 192 publications receiving 9442 citations. Previous affiliations of Aeron C. Hurt include World Health Organization & University of Melbourne.
Papers published on a yearly basis
Papers
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TL;DR: There was continuous circulation in east and Southeast Asia via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year, suggesting that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution.
Abstract: Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
689 citations
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TL;DR: Single‐dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superiorto both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.
Abstract: Background Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infection...
562 citations
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TL;DR: The findings of Koel et al. (p. 976) show that major antigenic change can be caused by single amino acid substitutions, which substantially skew the way the immune system “sees” the virus.
Abstract: The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
486 citations
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Fred Hutchinson Cancer Research Center1, National Institutes of Health2, World Health Organization3, National Institute of Virology4, Centers for Disease Control and Prevention5, National Institute for Medical Research6, King Institute of Preventive Medicine and Research7, University of Cambridge8, Chinese Center for Disease Control and Prevention9, University of California, Los Angeles10, Katholieke Universiteit Leuven11
TL;DR: Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.
Abstract: Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.
433 citations
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TL;DR: The antibody landscape was introduced, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, and it was found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters.
Abstract: We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
340 citations
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TL;DR: Wild aquatic bird populations have long been considered the natural reservoir for influenza A viruses with virus transmission from these birds seeding other avian and mammalian hosts, but recent studies in bats have suggested other reservoir species may also exist.
4,155 citations
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TL;DR: The Discriminant Analysis of Principal Components (DAPC) is introduced, a multivariate method designed to identify and describe clusters of genetically related individuals that performs generally better than STRUCTURE at characterizing population subdivision.
Abstract: The dramatic progress in sequencing technologies offers unprecedented prospects for deciphering the organization of natural populations in space and time. However, the size of the datasets generated also poses some daunting challenges. In particular, Bayesian clustering algorithms based on pre-defined population genetics models such as the STRUCTURE or BAPS software may not be able to cope with this unprecedented amount of data. Thus, there is a need for less computer-intensive approaches. Multivariate analyses seem particularly appealing as they are specifically devoted to extracting information from large datasets. Unfortunately, currently available multivariate methods still lack some essential features needed to study the genetic structure of natural populations. We introduce the Discriminant Analysis of Principal Components (DAPC), a multivariate method designed to identify and describe clusters of genetically related individuals. When group priors are lacking, DAPC uses sequential K-means and model selection to infer genetic clusters. Our approach allows extracting rich information from genetic data, providing assignment of individuals to groups, a visual assessment of between-population differentiation, and contribution of individual alleles to population structuring. We evaluate the performance of our method using simulated data, which were also analyzed using STRUCTURE as a benchmark. Additionally, we illustrate the method by analyzing microsatellite polymorphism in worldwide human populations and hemagglutinin gene sequence variation in seasonal influenza. Analysis of simulated data revealed that our approach performs generally better than STRUCTURE at characterizing population subdivision. The tools implemented in DAPC for the identification of clusters and graphical representation of between-group structures allow to unravel complex population structures. Our approach is also faster than Bayesian clustering algorithms by several orders of magnitude, and may be applicable to a wider range of datasets.
3,770 citations
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Centers for Disease Control and Prevention1, University of Cambridge2, National Institutes of Health3, Erasmus University Rotterdam4, Naval Medical Center San Diego5, Arizona State University6, Colorado Department of Public Health and Environment7, Oklahoma State Department of Health8, Wadsworth Center9, Ohio Department of Health10, South Carolina Department of Health and Environmental Control11, Dallas County12, Baylor College of Medicine13, San Diego State University14, Centra15, California Health and Human Services Agency16, Marshfield Clinic17, Michigan Department of Community Health18
TL;DR: The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period as mentioned in this paper.
Abstract: Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).
2,393 citations
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TL;DR: Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients, and all three patients died.
Abstract: Background Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. Methods We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase–polymerase-chain-reaction assays, viral culturing, and sequence analyses. Results A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) virus...
2,113 citations