Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross
Year: 2020
Type: article
Abstract: 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.
Source: Cell Reports
Authors: Kelsey E. Noll, Alan C. Whitmore, Ande West, Mary K. McCarthy, Clayton R. Morrison, Kenneth S. Plante, Brea K. Hampton, Heike Kollmus, Carolin Pilzner, Sarah R. Leist, Lisa E. Gralinski, Vineet D. Menachery, Alexandra Schäfer, Darla Miller, Ginger Shaw, Michael Mooney, Shannon McWeeney, Fernando Pardo-Manuel de Villena, Klaus Schughart, Thomas E. Morrison, Ralph S. Baric, Martin T. Ferris, Mark T. Heise
Institutions: University of North Carolina at Chapel Hill, University of Colorado Anschutz, The University of Texas Medical Branch at Galveston, Helmholtz Centre for Infection Research, Oregon Health & Science University, OHSU Knight Cancer Institute, UNC Lineberger Comprehensive Cancer Center, University of Tennessee Health Science Center, University of Veterinary Medicine Hannover, Foundation
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1404469632, G1433686416, G1741978266, G2030458809, G2036853765, G2465947240, G2674753787, G2842840046, G3155764223, Center for Research in Diagnostics and Discovery, G5730991322, G633655172, G7010035400, G72655844, G7850341591, G7931190342, Chikungunya Pathogenesis in a Complex Population, Molecular Biology of Viral Diseases Predoctoral Training Grant, Human Cytomegalovirus dysregulation of host hematopoietic progenitor cell signaling pathways to modulate latency and reactivation, Infectious Disease Pathogenesis Research Training Program
OpenAlex ID: W3017683741