Ebola virus infection induces autoimmunity against dsDNA and HSP60.
Ebola virus (EBOV) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. Identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. In this study, using mouse and non-human primates which survived EBOV challenge, ELISA, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind their induction and monitor autoantibodies accumulation in various tissues. In infected mice and NHP, polyclonal B cell activation and autoantigens secretion induced autoantibodies against dsDNA and heat shock protein 60 as well as antibody accumulation in tissues associated with long-term clinical manifestations in humans. Finally, the presence of these autoantibodies was confirmed in human EBOV survivors. Overall, this study supports the concept that autoimmunity is a causative parameter that contributes to the various illnesses observed in EBOV survivors.
University of Manitoba, Winnipeg, Canada.|National Microbiology Laboratory, Public health Agency of Canada, Winnipeg, Canada.
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Fausther-Bovendo
University of Manitoba, Winnipeg, Canada.|National Microbiology Laboratory, Public health Agency of Canada, Winnipeg, Canada.
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Qiu
JC Wilt Infectious Disease Research Centre, Winnipeg, Canada.
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McCorrister
JC Wilt Infectious Disease Research Centre, Winnipeg, Canada.
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Westmacott
JC Wilt Infectious Disease Research Centre, Winnipeg, Canada.|National HIV and Retrovirology Laboratory, Ottawa, Canada.
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Sandstrom
Lazzaro Spallanzani, National Institute for Infectious Diseases-IRCCS, Rome, Italy.
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Castilletti
Lazzaro Spallanzani, National Institute for Infectious Diseases-IRCCS, Rome, Italy.
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Di Caro
Lazzaro Spallanzani, National Institute for Infectious Diseases-IRCCS, Rome, Italy.
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Ippolito
National Microbiology Laboratory, Public health Agency of Canada, Winnipeg, Canada.|Department of Pathology and Laboratory Medicine, University of Pennsylvania School 27 of Medicine, Philadelphia, PA, USA.|Laval University, Department of Microbiology and Immunology, Faculty of Medicine, Quebec, Canada.
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Kobinger
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D018834:Chaperonin 60 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000276:immunology; D029043:Ebolavirus / Q000276:immunology* / Q000472:pathogenicity; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics; D011323:Primates / Q000276:immunology / Q000821:virology; D017741:Survivors
D000914:Antibodies, Viral; D001323:Autoantibodies; D018834:Chaperonin 60; C557066:Hspd1 protein, mouse; D007074:Immunoglobulin G; D024101:Mitochondrial Proteins; D004247:DNA