title: Mimiviruses and the Human Interferon System: Viral Evasion of Classical Antiviral Activities, But Inhibition By a Novel Interferon-β Regulated Immunomodulatory Pathway.
abstract: In this review we discuss the role of mimiviruses as potential human pathogens focusing on clinical and evolutionary evidence. We also propose a novel antiviral immunomodulatory pathway controlled by interferon-β (IFN-β) and mediated by immune-responsive gene 1 (IRG1) and itaconic acid, its product. Acanthamoeba polyphaga Mimivirus (APMV) was isolated from amoebae in a hospital while investigating a pneumonia outbreak. Mimivirus ubiquity and role as protist pathogens are well understood, and its putative status as a human pathogen has been gaining strength as more evidence is being found. The study of APMV and human cells interaction revealed that the virus is able to evade the IFN system by inhibiting the regulation of interferon-stimulated genes, suggesting that the virus and humans have had host-pathogen interactions. It also has shown that the virus is capable of growing on IFN-α2, but not on IFN-β-treated cells, hinting at an exclusive IFN-β antiviral pathway. Our hypothesis based on preliminary data and published articles is that IFN-β preferentially upregulates IRG1 in human macrophagic cells, which in turn produces itaconic acid. This metabolite links metabolism to antiviral activity by inactivating the virus, in a novel immunomodulatory pathway relevant for APMV infections and probably to other infectious diseases as well.
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Jyvaskyla , Jyvaskyla, Finland .
authors.forename: Gabriel Magno de Freitas
authors.initials: GM
authors.lastname: Almeida
authors.affiliation: 2 Laboratorio de Virus, Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Lorena C Ferreira
authors.initials: LC
authors.lastname: Silva
authors.affiliation: 3 Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Universite Faculté de Médecine , Marseille, France .
authors.forename: Philippe
authors.initials: P
authors.lastname: Colson
authors.affiliation: 2 Laboratorio de Virus, Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .|3 Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Universite Faculté de Médecine , Marseille, France .
authors.forename: Jonatas Santos
authors.initials: JS
authors.lastname: Abrahao
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases; D004266:DNA Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000821:virology*; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D016899:Interferon-beta / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D056686:Mimiviridae / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013386:Succinates / Q000378:metabolism
chemical_list: D011506:Proteins; D013386:Succinates; D016899:Interferon-beta; D007372:Interferons; C561544:ACOD1 protein, human; D002262:Carboxy-Lyases; C005229:itaconic acid
keywords: APMV; IFN-β; IRG1; giant virus; immunometabolism; interferon beta; itaconic acid; mimivirus