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Title: Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection
Authors: MacDuff, Donna A.
Reese, Tiffany A.
Kimmey, Jacqueline M.
Weiss, Leslie A.
Song, Christina
Zhang, Xin
Kambal, Amal
Duan, Erning
Carrero, Javier A.
Boisson, Bertrand
Laplantine, Emmanuel
Israel, Alain
Picard, Capucine
Colonna, Marco
Edelson, Brian T.
Sibley, L. David
Stallings, Christina L.
Casanova, Jean Laurent
Iwai, Kazuhiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Virgin, Herbert W.
Author's alias: 岩井, 一宏
Issue Date: 20-Jan-2015
Publisher: eLife Sciences Publications Ltd
Journal title: eLife
Volume: 4
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.
Rights: Copyright MacDuff et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI(Published Version): 10.7554/eLife.04494
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