Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice. Export

@article{citeulike:5726609, 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 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.}, author = {Boon, Adrianus Cm C. and Debeauchamp, Jennifer and Hollmann, Anna and Luke, Jennifer and Kotb, Malak and Rowe, Sarah and Finkelstein, David and Neale, Geoffrey and Lu, Lu and Williams, Robert W. and Webby, Richard J.}, citeulike-article-id = {5726609}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/JVI.00514-09}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19706712}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19706712}, day = {12}, doi = {10.1128/JVI.00514-09}, issn = {1098-5514}, journal = {Journal of virology}, keywords = {avian, h5n1, host, influenza}, month = {August}, posted-at = {2009-09-05 15:41:55}, priority = {2}, title = {Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice.}, url = {http://dx.doi.org/10.1128/JVI.00514-09}, year = {2009} }

TY - JOUR ID - citeulike:5726609 L3 - citeulike-article-id:5726609 N2 - 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. JF - Journal of virology SN - 1098-5514 TI - Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice. KW - avian KW - h5n1 KW - host KW - influenza AU - Boon, Adrianus Cm AU - Debeauchamp, Jennifer AU - Hollmann, Anna AU - Luke, Jennifer AU - Kotb, Malak AU - Rowe, Sarah AU - Finkelstein, David AU - Neale, Geoffrey AU - Lu, Lu AU - Williams, Robert AU - Webby, Richard PY - 2009/08/12/ UR - http://dx.doi.org/10.1128/JVI.00514-09 ER -