Giuseppe
Emeritus
J Virol. 2009 Aug 12. [Epub ahead of print]
Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice.
Boon AC, Debeauchamp J, Hollmann A, Luke J, Kotb M, Rowe S, Finkelstein D, Neale G, Lu L, Williams RW, Webby RJ. - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis TN 38105, USA; Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis TN, 38105, USA; VA Medical Center and MidSouth Center for Biodefense and Security, Memphis TN, 38104, USA; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
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 pro-inflammatory cytokines CCL2 and TNF-alpha in susceptible DBA/2J mice. Gene mapping with recombinant inbred BXD strains revealed five loci or Qivr (Quantitative trait locus 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, hemolytic complement, affected virus titer 7 days after infection. We conclude that H5N1 influenza virus induced pathology is affected by a complex and multigenic host component.
PMID: 19706712 [PubMed - as supplied by publisher]
-
------
Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice.
Boon AC, Debeauchamp J, Hollmann A, Luke J, Kotb M, Rowe S, Finkelstein D, Neale G, Lu L, Williams RW, Webby RJ. - Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis TN 38105, USA; Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis TN, 38105, USA; VA Medical Center and MidSouth Center for Biodefense and Security, Memphis TN, 38104, USA; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
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 pro-inflammatory cytokines CCL2 and TNF-alpha in susceptible DBA/2J mice. Gene mapping with recombinant inbred BXD strains revealed five loci or Qivr (Quantitative trait locus 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, hemolytic complement, affected virus titer 7 days after infection. We conclude that H5N1 influenza virus induced pathology is affected by a complex and multigenic host component.
PMID: 19706712 [PubMed - as supplied by publisher]
-
------