tetano
Editor, Senior Moderator
J Virol. 2010 Jul 14. [Epub ahead of print]
Assessing the viral fitness of oseltamivir-resistant influenza viruses in ferrets using a competitive mixtures model.
Hurt AC, Nor'e SS, McCaw JM, Fryer HR, Mosse J, McLean AR, Barr IG.
WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St, North Melbourne, Victoria 3051, Australia; Monash University, School of Applied Sciences, Churchill, Victoria 3842, Australia; Vaccine and Immunisation Research Group, University of Melbourne, Melbourne School of Population Health and Murdoch Childrens Research Institute, Royal Childrens Hospital, Melbourne, Victoria 3010, Australia; University of Oxford, Department of Zoology, Institute for Emergent Infections of Humans, James Martin 21 Century School, Oxford OX1 3PS, United Kingdom.
Abstract
To determine the relative fitness of oseltamivir-resistant strains compared to susceptible wild-type viruses, we combined mathematical modelling and statistical techniques with a novel in vivo 'competitive mixtures' experimental model. Ferrets were co-infected with either pure populations (100% susceptible wild-type or 100% oseltamivir-resistant mutant virus) or mixed populations of wild-type and oseltamivir-resistant influenza viruses (80%:20%, 50%:50%, 20%:80%) at equivalent infectivity titres, and the changes in the relative proportion of those two viruses were monitored over the course of the infection within-host and over host-to-host transmission events in a ferret contact model. Co-infection of ferrets with mixtures of an oseltamivir-resistant R292K mutant A(H3N2) virus and a R292 oseltamivir-susceptible wild-type virus, demonstrated that the R292K mutant virus was rapidly outgrown by the R292 wild-type virus in artificially infected donor ferrets, and did not transmit to any of the recipient ferrets. The competitive mixtures model was also used to investigate the fitness of the seasonal A(H1N1) oseltamivir-resistant H274Y mutant, and showed that within infected ferrets the H274Y mutant virus was marginally outgrown by the wild type strain, but demonstrated equivalent transmissibility between ferrets. This novel in vivo experimental method and accompanying mathematical analysis provides greater insight into the relative fitness, both within the host and between hosts, of two different influenza strains compared to more traditional methods that infect ferrets with only pure populations of viruses. Our statistical inferences are essential for the development of the next generation of mathematical models of the emergence and spread of oseltamivir-resistant influenza in human populations.
PMID: 20631138 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20631138
Assessing the viral fitness of oseltamivir-resistant influenza viruses in ferrets using a competitive mixtures model.
Hurt AC, Nor'e SS, McCaw JM, Fryer HR, Mosse J, McLean AR, Barr IG.
WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St, North Melbourne, Victoria 3051, Australia; Monash University, School of Applied Sciences, Churchill, Victoria 3842, Australia; Vaccine and Immunisation Research Group, University of Melbourne, Melbourne School of Population Health and Murdoch Childrens Research Institute, Royal Childrens Hospital, Melbourne, Victoria 3010, Australia; University of Oxford, Department of Zoology, Institute for Emergent Infections of Humans, James Martin 21 Century School, Oxford OX1 3PS, United Kingdom.
Abstract
To determine the relative fitness of oseltamivir-resistant strains compared to susceptible wild-type viruses, we combined mathematical modelling and statistical techniques with a novel in vivo 'competitive mixtures' experimental model. Ferrets were co-infected with either pure populations (100% susceptible wild-type or 100% oseltamivir-resistant mutant virus) or mixed populations of wild-type and oseltamivir-resistant influenza viruses (80%:20%, 50%:50%, 20%:80%) at equivalent infectivity titres, and the changes in the relative proportion of those two viruses were monitored over the course of the infection within-host and over host-to-host transmission events in a ferret contact model. Co-infection of ferrets with mixtures of an oseltamivir-resistant R292K mutant A(H3N2) virus and a R292 oseltamivir-susceptible wild-type virus, demonstrated that the R292K mutant virus was rapidly outgrown by the R292 wild-type virus in artificially infected donor ferrets, and did not transmit to any of the recipient ferrets. The competitive mixtures model was also used to investigate the fitness of the seasonal A(H1N1) oseltamivir-resistant H274Y mutant, and showed that within infected ferrets the H274Y mutant virus was marginally outgrown by the wild type strain, but demonstrated equivalent transmissibility between ferrets. This novel in vivo experimental method and accompanying mathematical analysis provides greater insight into the relative fitness, both within the host and between hosts, of two different influenza strains compared to more traditional methods that infect ferrets with only pure populations of viruses. Our statistical inferences are essential for the development of the next generation of mathematical models of the emergence and spread of oseltamivir-resistant influenza in human populations.
PMID: 20631138 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20631138