51. Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross
- Author
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Ande West, Shannon K. McWeeney, Brea K. Hampton, Fernando Pardo-Manuel de Villena, Clayton R. Morrison, Carolin Pilzner, Alan C. Whitmore, Ralph S. Baric, Alexandra Schäfer, Martin T. Ferris, Kelsey E. Noll, Kenneth S. Plante, Mary K. McCarthy, Heike Kollmus, Ginger D. Shaw, Klaus Schughart, Vineet D. Menachery, Darla R. Miller, Mark T. Heise, Lisa E. Gralinski, Sarah R. Leist, Michael Mooney, and Thomas E. Morrison
- Subjects
0301 basic medicine ,Candidate gene ,Disease ,medicine.disease_cause ,Virus Replication ,General Biochemistry, Genetics and Molecular Biology ,Article ,Collaborative Cross ,influenza virus ,03 medical and health sciences ,0302 clinical medicine ,Gene mapping ,humoral immunity ,antibody ,Influenza, Human ,Influenza A virus ,medicine ,Humans ,Gene ,lcsh:QH301-705.5 ,Genetics ,genetic reference population ,biology ,genetic architecture ,Genetic architecture ,030104 developmental biology ,host genetics ,complex trait ,lcsh:Biology (General) ,Humoral immunity ,Host-Pathogen Interactions ,biology.protein ,genetic mapping ,Antibody ,influenza ,030217 neurology & neurosurgery - Abstract
Summary Host genetic factors play a fundamental role in regulating humoral immunity to viral infection, including influenza A virus (IAV). Here, we utilize the Collaborative Cross (CC), a mouse genetic reference population, to study genetic regulation of variation in antibody response following IAV infection. CC mice show significant heritable variation in the magnitude, kinetics, and composition of IAV-specific antibody response. We map 23 genetic loci associated with this variation. Analysis of a subset of these loci finds that they broadly affect the antibody response to IAV as well as other viruses. Candidate genes are identified based on predicted variant consequences and haplotype-specific expression patterns, and several show overlap with genes identified in human mapping studies. These findings demonstrate that the host antibody response to IAV infection is under complex genetic control and highlight the utility of the CC in modeling and identifying genetic factors with translational relevance to human health and disease., Graphical Abstract, Highlights • Humoral response to influenza A virus varies across genetically diverse mice • Distinct genetic loci are important for different aspects of the humoral response • Loci that regulate antibody to influenza are also important for other pathogens • Comparison across datasets informs rational selection of candidate genes, Noll et al. use the Collaborative Cross, a mouse genetic reference population, to map genetic loci associated with variation in the humoral response to influenza virus infection. Cross-dataset comparison shows that mapped loci are important for antibody response to multiple pathogens, and candidate genes with likely translational relevance are identified.
- Published
- 2020