Multiple genes contribute to the virulent phenotype observed in ferrets of an H5N1 influenza virus isolated from Thailand in 2004.

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

Virology

journal_title

Virology

authors

Maines TR,Chen LM,Belser JA,Van Hoeven N,Smith E,Donis RO,Tumpey TM,Katz JM

doi

10.1016/j.virol.2011.02.005

subject

Has Abstract

pub_date

2011-05-10 00:00:00

pages

226-30

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(11)00066-3

journal_volume

413

pub_type

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