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WHO Collaborating Centre for Reference and Research on Influenza (VIDRL)
Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne VIC 3000 Australia

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Antivirals and Animal Influenza Viruses

A/Prof Aeron Hurt
Senior Research Scientist
Honorary Principal Research Fellow, Department of Microbiology and Immunology, The University of Melbourne

Email: aeron.hurt@influenzacentre.org

Research Interests

  1. Antiviral drug resistance: Using both seasonal human influenza viruses and viruses of pandemic potential, such as highly pathogenic A(H5N1), we are interested in the mutations that arise under selection pressure of different influenza antivirals, how readily they arise and their effect on susceptibility and viral function.
    Related publications

  2. Novel influenza antivirals: We are interested in working with licensed influenza antivirals, as well as those in late phase clinical trials around the world. Currently these include projects related to four neuraminidase inhibitors: oseltamivir, zanamivir, peramivir and laninamivir; a polymerase inhibitor, favipiravir (T-705); and nitzoxanide.a repurposed drug with anti-influenza activity.
    Related publications

  3. Use of in vivo models: We use a ferret infection model to asses various aspects of antiviral drug effectiveness, optimal treatment strategies and the effect of resistance mutations on viral replication and transmissibility.
    Related publications

Animal influenza viruses
  1. Avian influenza surveillance of wild birds: Together with collaborators we conduct surveillance of wild birds for avian influenza viruses throughout Australia and even conduct surveillance of penguins in Antarctica! Detection, molecular and functional analysis of strains leads to better understanding of the evolution and ecology of avian influenza viruses.
    Related publications

  2. In vivo transmissibility of avian and swine influenza viruses: Using the ferret model we can better understand the pathogenicity, replication kinetics and transmissibility of avian or swine influenza viruses. Such information is important to predict the risk that these animal influenza viruses pose to humans and their likelihood for sustained human-to-human spread.
    Related publications

Research projects: The effectiveness of antiviral treatment in influenza infections
We currently have projects available for Honours, Masters or PhD students. Please contact Aeron Hurt at aeron.hurt@influenzacentre.org if you would like to find out more about these projects.

The influenza antiviral drug, oseltamivir (Tamiflu), is widely prescribed and has been stockpiled by many countries, including Australia, for use in a future pandemic to treat influenza infection. However, in recent years the effectiveness of the drug has been hotly debated. Sole reliance on this class of antivirals (neuraminidase inhibitor) means that there is an urgent need to characterise the effectiveness of other antivirals for influenza. This project will incorporate both in vitro and in vivo techniques to study the effect of different antivirals on viral replication, pathogenesis, transmission and drug resistance. In vitro techniques involve real-time PCR, Sanger sequencing, cell culture based inhibition assay and viral growth kinetics studies. For in vivo assessment, an established ferret model of influenza infection will be used to determine the effectiveness of different treatment strategies. Immunological and metabolomics assessment involving RNA sequencing and metabolomics analysis will be used to further elicit the mechanism of how the antivirals ameliorate influenza infection.

Laboratory techniques
  • Molecular biology: reverse genetics; site-directed mutagenesis; cloning; pyrosequencing and Sanger sequencing
  • Classical virology and functional techniques: cell culture; virus culture; plaquing; TCID50; haemagglutination-inhibition; neuraminidase inhibition assays
  • Ferret models of influenza infection: intranasal, intratrachael and intraocular infection; nasal washes; antiviral drug administration; morbidity measurements
Related publications
Antiviral drug resistance:
Meijer A, Rebelo-de-Andrade H, Correia V, Besselaar T, Drager-Dayal R, Fry A, Gregory V, Gubareva L, Kageyama T, Lackenby A, Lo J, Odagiri T, Pereyaslov D, Siqueira MM, Takashita E, Tashiro M, Wang D, Wong S, Zhang W, Daniels RS, Hurt AC. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013. Antiviral Res. 2014 Oct;110:31-41. doi: 10.1016/j.antiviral.2014.07.001. PubMed link

Hurt AC, Leang SK, Tiedemann K, Butler J, Mechinaud F, Kelso A, Downie P, Barr IG. Progressive emergence of an oseltamivir-resistant A(H3N2) virus over two courses of oseltamivir treatment in an immunocompromised paediatric patient. Influenza Other Respir Viruses. 2013 Nov;7(6):904-8. doi: 10.1111/irv.12108. PubMed link

Leang SK, Deng YM, Shaw R, Caldwell N, Iannello P, Komadina N, Buchy P, Chittaganpitch M, Dwyer DE, Fagan P, Gourinat AC, Hammill F, Horwood PF, Huang QS, Ip PK, Jennings L, Kesson A, Kok T, Kool JL, Levy A, Lin C, Lindsay K, Osman O, Papadakis G, Rahnamal F, Rawlinson W, Redden C, Ridgway J, Sam IC, Svobodova S, Tandoc A, Wickramasinghe G, Williamson J, Wilson N, Yusof MA, Kelso A, Barr IG, Hurt AC. Influenza antiviral resistance in the Asia-Pacific region during 2011. Antiviral Res. 2013 Feb;97(2):206-10. doi: 10.1016/j.antiviral.2012.12.016. PubMed link

Meijer A, Jonges M, van Beek P, Swaan CM, Osterhaus AD, Daniels RS, Hurt AC, Koopmans MP. Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning from Spain, August 2012. Euro Surveill. 2012 Sep 6;17(36):20266. PubMed link

Wang B, Taylor J, Ratnamohan M, McPhie K, Kesson A, Dixit R, Booy R, Hurt A, Saksena N, Dwyer DE. Frequency of oseltamivir resistance in Sydney, during the Newcastle outbreak of community transmitted oseltamivir-resistant influenza A(H1N1)pdm09 virus, Australia, June to August 2011. Euro Surveill. 2012 Jul 5;17(27). pii: 20210. PubMed link

Hurt AC, Hardie K, Wilson NJ, Deng YM, Osbourn M, Leang SK, Lee RT, Iannello P, Gehrig N, Shaw R, Wark P, Caldwell N, Givney RC, Xue L, Maurer-Stroh S, Dwyer DE, Wang B, Smith DW, Levy A, Booy R, Dixit R, Merritt T, Kelso A, Dalton C, Durrheim D, Barr IG. Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia. J Infect Dis. 2012 Jul 15;206(2):148-57. doi: 10.1093/infdis/jis337. PubMed link

Hurt AC, Leang SK, Speers DJ, Barr IG, Maurer-Stroh S. Mutations I117V and I117M and oseltamivir sensitivity of pandemic (H1N1) 2009 viruses. Emerg Infect Dis. 2012 Jan;18(1):109-12. doi: 10.3201/eid1801.111079. PubMed link

Hurt AC, Hardie K, Wilson NJ, Deng YM, Osbourn M, Gehrig N, Kelso A. Community transmission of oseltamivir-resistant A(H1N1)pdm09 influenza. N Engl J Med. 2011 Dec 29;365(26):2541-2. doi: 10.1056/NEJMc1111078. PubMed link

Hurt AC, Lee RT, Leang SK, Cui L, Deng YM, Phuah SP, Caldwell N, Freeman K, Komadina N, Smith D, Speers D, Kelso A, Lin RT, Maurer-Stroh S, Barr IG. Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation. Euro Surveill. 2011 Jun 9;16(23). pii: 19884. Erratum in: Euro Surveill. 2011;16(27). pii: 19909. PubMed link

Hurt AC, Deng YM, Ernest J, Caldwell N, Leang L, Iannello P, Komadina N, Shaw R, Smith D, Dwyer DE, Tramontana AR, Lin RT, Freeman K, Kelso A, Barr IG. Oseltamivir-resistant influenza viruses circulating during the first year of the influenza A(H1N1) 2009 pandemic in the Asia-Pacific region, March 2009 to March 2010. Euro Surveill. 2011 Jan 20;16(3). pii: 19770. PubMed link

Tramontana AR, George B, Hurt AC, Doyle JS, Langan K, Reid AB, Harper JM, Thursky K, Worth LJ, Dwyer DE, Morrissey CO, Johnson PD, Buising KL, Harrison SJ, Seymour JF, Ferguson PE, Wang B, Denholm JT, Cheng AC, Slavin M. Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerg Infect Dis. 2010 Jul;16(7):1068-75. doi: 10.3201/eid1607.091691. PubMed link

Novel influenza antivirals:
Leang SK, Kwok S, Sullivan SG, Maurer-Stroh S, Kelso A, Barr IG, Hurt AC. Peramivir and laninamivir susceptibility of circulating influenza A and B viruses. Influenza Other Respir Viruses. 2014 Mar;8(2):135-9. PubMed link

Doyle TM, Li C, Bucher DJ, Hashem AM, Van Domselaar G, Wang J, Farnsworth A, She YM, Cyr T, He R, Brown EG, Hurt AC, Li X. A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains. Biochem Biophys Res Commun. 2013 Nov 8;441(1):226-9. doi: 10.1016/j.bbrc.2013.10.041. PubMed link

Doyle TM, Hashem AM, Li C, Van Domselaar G, Larocque L, Wang J, Smith D, Cyr T, Farnsworth A, He R, Hurt AC, Brown EG, Li X. Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Res. 2013 Nov;100(2):567-74. doi: 10.1016/j.antiviral.2013.09.018. PubMed link

Use of in vivo models:
Oh DY, Lowther S, McCaw JM, Sullivan SG, Leang SK, Haining J, Arkinstall R, Kelso A, Mcvernon J, Barr IG, Middleton D, Hurt AC. Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact. J Antimicrob Chemother. 2014 Sep;69(9):2458-69. doi: 10.1093/jac/dku146. PubMed link

Butler J, Hooper KA, Petrie S, Lee R, Maurer-Stroh S, Reh L, Guarnaccia T, Baas C, Xue L, Vitesnik S, Leang SK, McVernon J, Kelso A, Barr IG, McCaw JM, Bloom JD, Hurt AC. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses. PLoS Pathog. 2014 Apr 3;10(4):e1004065. doi: 10.1371/journal.ppat.1004065. eCollection 2014 Apr. PubMed link

Petrie SM, Guarnaccia T, Laurie KL, Hurt AC, McVernon J, McCaw JM. Reducing uncertainty in within-host parameter estimates of influenza infection by measuring both infectious and total viral load. PLoS One. 2013 May 15;8(5):e64098. doi: 10.1371/journal.pone.0064098. Print 2013. Erratum in: PLoS One. 2013;8(11). doi:10.1371/annotation/3b815950-b0eb-4aac-9a83-e92f830f844b. PubMed link

McCaw JM, Arinaminpathy N, Hurt AC, McVernon J, McLean AR. A mathematical framework for estimating pathogen transmission fitness and inoculum size using data from a competitive mixtures animal model. PLoS Comput Biol. 2011 Apr;7(4):e1002026. doi: 10.1371/journal.pcbi.1002026. PubMed link

Hurt AC, Lowther S, Middleton D, Barr IG. Assessing the development of oseltamivir and zanamivir resistance in A(H5N1) influenza viruses using a ferret model. Antiviral Res. 2010 Sep;87(3):361-6. doi: 10.1016/j.antiviral.2010.06.009. PubMed link

Avian influenza surveillance of wild birds:
Hurt AC, Vijaykrishna D, Butler J, Baas C, Maurer-Stroh S, Silva-de-la-Fuente MC, Medina-Vogel G, Olsen B, Kelso A, Barr IG, González-Acuña D. Detection of evolutionarily distinct avian influenza A viruses in Antarctica. MBio. 2014 May 6;5(3):e01098-14. doi: 10.1128/mBio.01098-14. PubMed link

Vijaykrishna D, Deng YM, Su YC, Fourment M, Iannello P, Arzey GG, Hansbro PM, Arzey KE, Kirkland PD, Warner S, O'Riley K, Barr IG, Smith GJ, Hurt AC. The recent establishment of North American H10 lineage influenza viruses in Australian wild waterfowl and the evolution of Australian avian influenza viruses. J Virol. 2013 Sep;87(18):10182-9. doi: 10.1128/JVI.03437-12. PubMed link

Arzey GG, Kirkland PD, Arzey KE, Frost M, Maywood P, Conaty S, Hurt AC, Deng YM, Iannello P, Barr I, Dwyer DE, Ratnamohan M, McPhie K, Selleck P. Influenza virus A(H10N7) in chickens and poultry abattoir workers, Australia. Emerg Infect Dis. 2012 May;18(5):814-6. doi: 10.3201/eid1805.111852. PubMed link

Hansbro PM, Warner S, Tracey JP, Arzey KE, Selleck P, O'Riley K, Beckett EL, Bunn C, Kirkland PD, Vijaykrishna D, Olsen B, Hurt AC. Surveillance and analysis of avian influenza viruses, Australia. Emerg Infect Dis. 2010 Dec;16(12):1896-904. doi: 10.3201/eid1612.100776. PubMed link

In vivo transmissibility of avian and swine influenza viruses:
Crispe E, Finlaison DS, Hurt AC, Kirkland PD. Infection of dogs with equine influenza virus: evidence for transmission from horses during the Australian outbreak. Aust Vet J. 2011 Jul;89 Suppl 1:27-8. doi: 10.1111/j.1751-0813.2011.00734.x. PubMed link

Hurt AC, Nor'e SS, McCaw JM, Fryer HR, Mosse J, McLean AR, Barr IG. Assessing the viral fitness of oseltamivir-resistant influenza viruses in ferrets, using a competitive-mixtures model. J Virol. 2010 Sep;84(18):9427-38. doi: 10.1128/JVI.00373-10. PubMed link

All relevant publications (PubMed listing)
All publications from the Centre

Epidemiology group
Early immune response group

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