{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["4"],"submitter":["MacDuff DA"],"funding":["Crohn's and Colitis Foundation of America","National Institute of Allergy and Infectious Diseases","National Center for Research Resources","Broad Foundation","Burroughs Wellcome Fund","March of Dimes Foundation","Edward Mallinckrodt Jr Foundation","National Institutes of Health","National Institute of General Medical Sciences","Arnold and Mabel Beckman Foundation","National Science Foundation"],"pubmed_abstract":["Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies."],"journal":["eLife"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4298697"],"repository":["biostudies-literature"],"pubmed_title":["Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection."],"pmcid":["PMC4298697"],"funding_grant_id":["DGE-1143954","5P01 AI061093","Private Grant","8UL1TR000043","Career Award for Medical Scientists","IBD-0357","Basil O'Conner Starter Scholar Research Award","R01 AI084887","Genetics Initiative grant 274415","U19 AI109725","AI036629","Beckman Young Investigator Award","GM007067","AI062832"],"pubmed_authors":["Picard C","Sibley LD","Boisson B","Kimmey JM","Colonna M","MacDuff DA","Song C","Weiss LA","Duan E","Casanova JL","Edelson BT","Iwai K","Kambal A","Israel A","Carrero JA","Stallings CL","Zhang X","Reese TA","Laplantine E","Virgin HW"],"additional_accession":[]},"is_claimable":false,"name":"Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.","description":"Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jan","modification":"2024-11-19T20:25:08.924Z","creation":"2019-06-06T13:44:19Z"},"accession":"S-EPMC4298697","cross_references":{"pubmed":["25599590"],"doi":["10.7554/eLife.04494"]}}