Multiple genes contribute to the virulent phenotype observed in ferrets of an H5N1 influenza virus isolated from Thailand in 2004.
Summary of "Multiple genes contribute to the virulent phenotype observed in ferrets of an H5N1 influenza virus isolated from Thailand in 2004."
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.
Affiliation
Journal Details
This article was published in the following journal.
Name: Virology
ISSN: 1096-0341
Pages: 226-30
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21388650
- DOI: http://dx.doi.org/10.1016/j.virol.2011.02.005
Medical and Biotech [MESH] Definitions
Genes, Recessive
Genes that influence the PHENOTYPE only in the homozygous state.
Genes, Dominant
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
Antley-bixler Syndrome Phenotype
An inherited condition characterized by multiple malformations of CARTILAGE and bone including CRANIOSYNOSTOSIS; midface hypoplasia; radiohumeral SYNOSTOSIS; CHOANAL ATRESIA; femoral bowing; neonatal fractures; and multiple joint CONTRACTURES and, occasionally, urogenital, gastrointestinal or cardiac defects. In utero exposure to FLUCONAZOLE, as well as mutations in at least two separate genes are associated with this condition - POR (encoding P450 (cytochrome) oxidoreductase (NADPH-FERRIHEMOPROTEIN REDUCTASE)) and FGFR2 (encoding FIBROBLAST GROWTH FACTOR RECEPTOR 2).
Influenza A Virus, H5n1 Subtype
A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 5 and neuraminidase 1. The H5N1 subtype, frequently referred to as the bird flu virus, is endemic in wild birds and very contagious among both domestic (POULTRY) and wild birds. It does not usually infect humans, but some cases have been reported.
Drug Resistance, Multiple, Fungal
The ability of fungi to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutations.
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