Abstract:
:Human infections with highly pathogenic H5N1 avian influenza viruses continue to occur in many parts of the world and pose a considerable public health threat. With the use of animal models, the identification of virulence determinants has been instrumental in improving our understanding of how these viruses cause severe disease in humans. Two genetically similar H5N1 viruses (A/Thailand/16/2004 and A/Thailand/SP83/2004) exhibit high or low virulence phenotypes, respectively, in multiple animal models. Reassortant viruses were generated from this virus pair and evaluated in ferrets. Each of the polymerase genes of A/Thailand/16/2004 virus individually conferred increased virulence to A/Thailand/SP83/2004 virus while the neuraminidase of the low virulence virus reduced virulence and replication efficiency of the virulent virus in ferrets unless the homologous HA was present. Our results demonstrate that H5N1 virus virulence determinants are polygenic and that there is an important correlation between polymerase adaptation, efficient replication in the host, and virulence.
journal_name
Virologyjournal_title
Virologyauthors
Maines TR,Chen LM,Belser JA,Van Hoeven N,Smith E,Donis RO,Tumpey TM,Katz JMdoi
10.1016/j.virol.2011.02.005subject
Has Abstractpub_date
2011-05-10 00:00:00pages
226-30issue
2eissn
0042-6822issn
1096-0341pii
S0042-6822(11)00066-3journal_volume
413pub_type
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