Aeron C. Hurt
University of Melbourne
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Featured researches published by Aeron C. Hurt.
Science | 2008
Colin A. Russell; Terry C. Jones; Ian G. Barr; Nancy J. Cox; Rebecca Garten; Vicky Gregory; Ian D. Gust; Alan W. Hampson; Alan J. Hay; Aeron C. Hurt; Jan C. de Jong; Anne Kelso; Alexander Klimov; Tsutomu Kageyama; Naomi Komadina; Alan S. Lapedes; Yi P. Lin; Ana Mosterin; Masatsugu Obuchi; Takato Odagiri; Albert D. M. E. Osterhaus; Michael Shaw; Eugene Skepner; Klaus Stöhr; Masato Tashiro; Ron A. M. Fouchier; Derek J. Smith
Antigenic and genetic analysis of the hemagglutinin of ∼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.
Science | 2013
Björn Koel; David F. Burke; Theo M. Bestebroer; Stefan van der Vliet; Gerben C. M. Zondag; Gaby Vervaet; Eugene Skepner; Nicola S. Lewis; Monique I. Spronken; Colin A. Russell; Mikhail Yurievich Eropkin; Aeron C. Hurt; Ian G. Barr; Jan C. de Jong; Albert D. M. E. Osterhaus; Ron A. M. Fouchier; Derek J. Smith
Flu Drift Limited Five antigenic sites in the virus surface hemagglutinin protein, which together comprise 131 amino acid positions, are thought to determine the full scope of antigenic drift of influenza A virus. Koel et al. (p. 976) show that major antigenic change can be caused by single amino acid substitutions. These single substitutions substantially skew the way the immune system “sees” the virus. All substitutions of importance are located next to the receptor-binding site in the hemagglutinin. Because there are few positions of importance for antigenic drift, there are strict biophysical limitations to the substitutions at these positions, which restricts the number of new antigenic drift variants at any point in time. Thus, the evolution of influenza virus may be more predictable than previously thought. The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site. 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.
Antiviral Research | 2009
Aeron C. Hurt; Joanne Ernest; Yi-Mo Deng; Pina Iannello; Terry G. Besselaar; Chris Birch; Philippe Buchy; Malinee Chittaganpitch; Shu-Chun Chiu; Dominic E. Dwyer; Aurélie Guigon; Bruce Harrower; Ip Peng Kei; Tuckweng Kok; Cui Lin; Ken McPhie; Apandi Mohd; Remigio M. Olveda; Tony Panayotou; William D. Rawlinson; Lesley Scott; David W. Smith; Holly D'Souza; Naomi Komadina; Robert D. Shaw; Anne Kelso; Ian G. Barr
The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them.
Journal of Virology | 2009
Aeron C. Hurt; Jessica K. Holien; Michael W. Parker; Anne Kelso; Ian G. Barr
ABSTRACT The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza A (H1N1) viruses in Europe, the United States, Oceania, and South Africa, to date there have been no reports of significant zanamivir resistance among influenza A (H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal influenza A (H1N1) viruses in Australasia and Southeast Asia. Analysis of 391 influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and Southeast Asia revealed nine viruses (2.3%) that demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible influenza A (H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wild-type virus in MDCK cells but equivalent infectivity and transmissibility in a ferret model.
Lancet Infectious Diseases | 2012
Aeron C. Hurt; Tawee Chotpitayasunondh; Nancy J. Cox; Rod S. Daniels; Alicia M. Fry; Larisa V. Gubareva; Frederick G. Hayden; David Sc Hui; Olav Hungnes; Angie Lackenby; Wilina Lim; Adam Meijer; Penn C; Masato Tashiro; Timothy M. Uyeki; Maria Zambon
Influenza A H1N1 2009 virus caused the first pandemic in an era when neuraminidase inhibitor antiviral drugs were available in many countries. The experiences of detecting and responding to resistance during the pandemic provided important lessons for public health, laboratory testing, and clinical management. We propose recommendations for antiviral susceptibility testing, reporting results, and management of patients infected with 2009 pandemic influenza A H1N1. Sustained global monitoring for antiviral resistance among circulating influenza viruses is crucial to inform public health and clinical recommendations for antiviral use, especially since community spread of oseltamivir-resistant A H1N1 2009 virus remains a concern. Further studies are needed to better understand influenza management in specific patient groups, such as severely immunocompromised hosts, including optimisation of antiviral treatment, rapid sample testing, and timely reporting of susceptibility results.
Nature | 2015
Trevor Bedford; Steven Riley; Ian G. Barr; Shobha Broor; Mandeep S. Chadha; Nancy J. Cox; Rodney S. Daniels; C Palani Gunasekaran; Aeron C. Hurt; Anne Kelso; Alexander Klimov; Nicola S. Lewis; Xiyan Li; John W. McCauley; Takato Odagiri; Varsha Potdar; Andrew Rambaut; Yuelong Shu; Eugene Skepner; Derek J. Smith; Marc A. Suchard; Masato Tashiro; Dayan Wang; Xiyan Xu; Philippe Lemey; Colin A. Russell
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.
Science | 2014
Judith M. Fonville; S. H. Wilks; Sarah Linda James; Annette Fox; Mario Ventresca; Malet Aban; L. Xue; T. C. Jones; N M H Le; Q T Pham; N D Tran; Y. Wong; Ana Mosterin; Leah C. Katzelnick; David Labonte; Thuy Le; G. van der Net; E. Skepner; Colin A. Russell; T. D. Kaplan; N. Masurel; J. C. de Jong; A. Palache; Walter Beyer; Q M Le; Thi Nguyen; Heiman Wertheim; Aeron C. Hurt; Albert D. M. E. Osterhaus; Ian G. Barr
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. Preemptive vaccine updates may substantially improve influenza vaccine efficacy in previously exposed individuals. [Also see Perspective by Lessler] Hills and valleys of influenza infection Each one of us may encounter several different strains of the ever-changing influenza virus during a lifetime. Scientists can now summarize such histories of infection over a lifetime of exposure. Fonville et al. visualize the interplay between protective responses and the evasive influenza virus by a technique called antibody landscape modeling (see the Perspective by Lessler). Landscapes reveal how exposure to new strains of the virus boost immune responses and indicate possibilities for optimizing future vaccination programs. Science, this issue p. 996; see also p. 919
Influenza and Other Respiratory Viruses | 2009
Aeron C. Hurt; Chantal Baas; Yi-Mo Deng; Sally Roberts; Anne Kelso; Ian G. Barr
Background In April 2009, an A(H1N1) influenza virus of swine lineage was detected in humans in the USA, and in just over a month has infected over 10 000 people in more than 40 countries.
Proceedings of the National Academy of Sciences of the United States of America | 2009
Carole Guillonneau; Justine D. Mintern; François Xavier Hubert; Aeron C. Hurt; Gurdyal S. Besra; Steven A. Porcelli; Ian G. Barr; Peter C. Doherty; Dale I. Godfrey; Stephen J. Turner
Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes and would thus be ineffective in the face of a pandemic caused by a novel variant emerging from, say, a wildlife reservoir. One possible solution would be to modify these vaccines so that they prime cross-reactive CD8+ cytotoxic T lymphocytes (CTL) cell-mediated immunity directed at conserved viral epitopes. A further strategy is to use novel adjuvants, such as the immunomodulatory glycolipid α-galactosylceramide (α-GalCer). We show here that giving α-GalCer with an inactivated influenza A virus has the paradoxical effect of diminishing acute CTL immunity via natural killer T (NKT) cell-dependent expression of indoleamine 2,3-dioxygenase (IDO), an important mediator of immune suppression, while at the same time promoting the survival of long-lived memory CTL populations capable of boosting protection against heterologous influenza A virus challenge. This enhancement of memory was likely due to the α-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of α-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8+ T cell memory.
Antiviral Research | 2014
Aeron C. Hurt; Terry G. Besselaar; Rod S. Daniels; Burcu Ermetal; Alicia M. Fry; Larisa V. Gubareva; Weijuan Huang; Angie Lackenby; Raphael Tze Chuen Lee; Janice Lo; Sebastian Maurer-Stroh; Ha T. Nguyen; Dmitriy Pereyaslov; Helena Rebelo-de-Andrade; Marilda M. Siqueira; Emi Takashita; Masato Tashiro; Danielle Tilmanis; Dayan Wang; Wenqing Zhang; Adam Meijer
The World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza (WHO CCs) tested 13,312 viruses collected by WHO recognized National Influenza Centres between May 2014 and May 2015 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Ninety-four per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.5% (n = 68) of viruses showed either highly reduced inhibition (HRI) or reduced inhibition (RI) (n = 56) against at least one of the four NAIs. Of the twelve viruses with HRI, six were A(H1N1)pdm09 viruses, three were A(H3N2) viruses and three were B/Yamagata-lineage viruses. The overall frequency of viruses with RI or HRI by the NAIs was lower than that observed in 2013–14 (1.9%), but similar to the 2012–13 period (0.6%). Based on the current analysis, the NAIs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections.