Distinct gene loci control the host response to influenza H1N1 virus infection in a time-dependent manner

2.50
Hdl Handle:
http://hdl.handle.net/10033/620755
Title:
Distinct gene loci control the host response to influenza H1N1 virus infection in a time-dependent manner
Authors:
Nedelko, Tatiana; Kollmus, Heike; Klawonn, Frank; Spijker, Sabine; Lu, Lu; Heßman, Manuela; Alberts, Rudi; Williams, Robert W; Schughart, Klaus
Abstract:
Abstract Background There is strong but mostly circumstantial evidence that genetic factors modulate the severity of influenza infection in humans. Using genetically diverse but fully inbred strains of mice it has been shown that host sequence variants have a strong influence on the severity of influenza A disease progression. In particular, C57BL/6J, the most widely used mouse strain in biomedical research, is comparatively resistant. In contrast, DBA/2J is highly susceptible. Results To map regions of the genome responsible for differences in influenza susceptibility, we infected a family of 53 BXD-type lines derived from a cross between C57BL/6J and DBA/2J strains with influenza A virus (PR8, H1N1). We monitored body weight, survival, and mean time to death for 13 days after infection. Qivr5 (quantitative trait for influenza virus resistance on chromosome 5) was the largest and most significant QTL for weight loss. The effect of Qivr5 was detectable on day 2 post infection, but was most pronounced on days 5 and 6. Survival rate mapped to Qivr5, but additionally revealed a second significant locus on chromosome 19 (Qivr19). Analysis of mean time to death affirmed both Qivr5 and Qivr19. In addition, we observed several regions of the genome with suggestive linkage. There are potentially complex combinatorial interactions of the parental alleles among loci. Analysis of multiple gene expression data sets and sequence variants in these strains highlights about 30 strong candidate genes across all loci that may control influenza A susceptibility and resistance. Conclusions We have mapped influenza susceptibility loci to chromosomes 2, 5, 16, 17, and 19. Body weight and survival loci have a time-dependent profile that presumably reflects the temporal dynamic of the response to infection. We highlight candidate genes in the respective intervals and review their possible biological function during infection.
Citation:
BMC Genomics. 2012 Aug 20;13(1):411
Issue Date:
20-Aug-2012
URI:
http://dx.doi.org/10.1186/1471-2164-13-411; http://hdl.handle.net/10033/620755
Type:
Journal Article
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authorNedelko, Tatianaen
dc.contributor.authorKollmus, Heikeen
dc.contributor.authorKlawonn, Franken
dc.contributor.authorSpijker, Sabineen
dc.contributor.authorLu, Luen
dc.contributor.authorHeßman, Manuelaen
dc.contributor.authorAlberts, Rudien
dc.contributor.authorWilliams, Robert Wen
dc.contributor.authorSchughart, Klausen
dc.date.accessioned2017-01-27T08:31:39Z-
dc.date.available2017-01-27T08:31:39Z-
dc.date.issued2012-08-20en
dc.identifier.citationBMC Genomics. 2012 Aug 20;13(1):411en
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2164-13-411en
dc.identifier.urihttp://hdl.handle.net/10033/620755-
dc.description.abstractAbstract Background There is strong but mostly circumstantial evidence that genetic factors modulate the severity of influenza infection in humans. Using genetically diverse but fully inbred strains of mice it has been shown that host sequence variants have a strong influence on the severity of influenza A disease progression. In particular, C57BL/6J, the most widely used mouse strain in biomedical research, is comparatively resistant. In contrast, DBA/2J is highly susceptible. Results To map regions of the genome responsible for differences in influenza susceptibility, we infected a family of 53 BXD-type lines derived from a cross between C57BL/6J and DBA/2J strains with influenza A virus (PR8, H1N1). We monitored body weight, survival, and mean time to death for 13 days after infection. Qivr5 (quantitative trait for influenza virus resistance on chromosome 5) was the largest and most significant QTL for weight loss. The effect of Qivr5 was detectable on day 2 post infection, but was most pronounced on days 5 and 6. Survival rate mapped to Qivr5, but additionally revealed a second significant locus on chromosome 19 (Qivr19). Analysis of mean time to death affirmed both Qivr5 and Qivr19. In addition, we observed several regions of the genome with suggestive linkage. There are potentially complex combinatorial interactions of the parental alleles among loci. Analysis of multiple gene expression data sets and sequence variants in these strains highlights about 30 strong candidate genes across all loci that may control influenza A susceptibility and resistance. Conclusions We have mapped influenza susceptibility loci to chromosomes 2, 5, 16, 17, and 19. Body weight and survival loci have a time-dependent profile that presumably reflects the temporal dynamic of the response to infection. We highlight candidate genes in the respective intervals and review their possible biological function during infection.en
dc.titleDistinct gene loci control the host response to influenza H1N1 virus infection in a time-dependent manneren
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderNedelko et al.; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:29:37Zen
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