title: MIMIVIRE is a defence system in mimivirus that confers resistance to virophage.
abstract: Since their discovery, giant viruses have revealed several unique features that challenge the conventional definition of a virus, such as their large and complex genomes, their infection by virophages and their presence of transferable short element transpovirons. Here we investigate the sensitivity of mimivirus to virophage infection in a collection of 59 viral strains and demonstrate lineage specificity in the resistance of mimivirus to Zamilon, a unique virophage that can infect lineages B and C of mimivirus but not lineage A. We hypothesized that mimiviruses harbour a defence mechanism resembling the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system that is widely present in bacteria and archaea. We performed de novo sequencing of 45 new mimivirus strains and searched for sequences specific to Zamilon in a total of 60 mimivirus genomes. We found that lineage A strains are resistant to Zamilon and contain the insertion of a repeated Zamilon sequence within an operon, here named the 'mimivirus virophage resistance element' (MIMIVIRE). Further analyses of the surrounding sequences showed that this locus is reminiscent of a defence mechanism related to the CRISPR-Cas system. Silencing the repeated sequence and the MIMIVIRE genes restores mimivirus susceptibility to Zamilon. The MIMIVIRE proteins possess the typical functions (nuclease and helicase) involved in the degradation of foreign nucleic acids. The viral defence system, MIMIVIRE, represents a nucleic-acid-based immunity against virophage infection.
authors.affiliation: Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.|IHU Méditerranée Infection, Pôle des Maladies Infectieuses, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Levasseur
authors.affiliation: Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.|IHU Méditerranée Infection, Pôle des Maladies Infectieuses, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Bekliz
authors.affiliation: Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.|IHU Méditerranée Infection, Pôle des Maladies Infectieuses, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chabrière
authors.affiliation: Aix-Marseille Université, CNRS, Centrale Marseille, I2M, UMR7373, FR 4213 - FR Eccorev 3098, équipe EBM, 13331 Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pontarotti
authors.affiliation: Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.|IHU Méditerranée Infection, Pôle des Maladies Infectieuses, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: La Scola
authors.affiliation: Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.|IHU Méditerranée Infection, Pôle des Maladies Infectieuses, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
mesh_terms: D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics; D056686:Mimiviridae / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D009876:Operon / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014780:Viruses / Q000235:genetics / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; D003851:Deoxyribonucleases; D004265:DNA Helicases