Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice

Adrianus C.M. Boon, Jennifer DeBeauchamp, Anna Hollmann, Jennifer Luke, Malak Kotb, Sarah Rowe, David Finkelstein, Geoffrey Neale, Lu Lu, Robert W. Williams, Richard J. Webby

Research output: Contribution to journalArticle

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Abstract

Despite the prevalence of H5N1 influenza viruses in global avian populations, comparatively few cases have been diagnosed in humans. Although viral factors almost certainly play a role in limiting human infection and disease, host genetics most likely contribute substantially. To model host factors in the context of influenza virus infection, we determined the lethal dose of a highly pathogenic H5N1 virus (A/Hong Kong/213/03) in C57BL/6J and DBA/2J mice and identified genetic elements associated with survival after infection. The lethal dose in these hosts varied by 4 logs and was associated with differences in replication kinetics and increased production of proinflammatory cytokines CCL2 and tumor necrosis factor alpha in susceptible DBA/2J mice. Gene mapping with recombinant inbred BXD strains revealed five loci or Qivr (quantitative trait loci for influenza virus resistance) located on chromosomes 2, 7, 11, 15, and 17 associated with resistance to H5N1 virus. In conjunction with gene expression profiling, we identified a number of candidate susceptibility genes. One of the validated genes, the hemolytic complement gene, affected virus titer 7 days after infection. We conclude that H5N1 influenza virus-induced pathology is affected by a complex and multigenic host component.

Original languageEnglish (US)
Pages (from-to)10417-10426
Number of pages10
JournalJournal of Virology
Volume83
Issue number20
DOIs
StatePublished - Oct 1 2009

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H5N1 Subtype Influenza A Virus
Influenza A virus
Orthomyxoviridae
Inbred DBA Mouse
genetic variation
lethal dose
mice
Infection
infection
Genes
Inborn Genetic Diseases
Chromosomes, Human, Pair 7
Chromosomes, Human, Pair 2
genes
Chromosome Mapping
Quantitative Trait Loci
Hong Kong
Gene Expression Profiling
Virus Diseases
viral load

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Boon, A. C. M., DeBeauchamp, J., Hollmann, A., Luke, J., Kotb, M., Rowe, S., ... Webby, R. J. (2009). Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice. Journal of Virology, 83(20), 10417-10426. https://doi.org/10.1128/JVI.00514-09

Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice. / Boon, Adrianus C.M.; DeBeauchamp, Jennifer; Hollmann, Anna; Luke, Jennifer; Kotb, Malak; Rowe, Sarah; Finkelstein, David; Neale, Geoffrey; Lu, Lu; Williams, Robert W.; Webby, Richard J.

In: Journal of Virology, Vol. 83, No. 20, 01.10.2009, p. 10417-10426.

Research output: Contribution to journalArticle

Boon, ACM, DeBeauchamp, J, Hollmann, A, Luke, J, Kotb, M, Rowe, S, Finkelstein, D, Neale, G, Lu, L, Williams, RW & Webby, RJ 2009, 'Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice', Journal of Virology, vol. 83, no. 20, pp. 10417-10426. https://doi.org/10.1128/JVI.00514-09
Boon, Adrianus C.M. ; DeBeauchamp, Jennifer ; Hollmann, Anna ; Luke, Jennifer ; Kotb, Malak ; Rowe, Sarah ; Finkelstein, David ; Neale, Geoffrey ; Lu, Lu ; Williams, Robert W. ; Webby, Richard J. / Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice. In: Journal of Virology. 2009 ; Vol. 83, No. 20. pp. 10417-10426.
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