title: IRGM is a common target of RNA viruses that subvert the autophagy network.
abstract: Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Isabel Pombo
authors.initials: IP
authors.lastname: Grégoire
authors.forename: Clémence
authors.initials: C
authors.lastname: Richetta
authors.forename: Laurène
authors.initials: L
authors.lastname: Meyniel-Schicklin
authors.forename: Sophie
authors.initials: S
authors.lastname: Borel
authors.forename: Fabrine
authors.initials: F
authors.lastname: Pradezynski
authors.forename: Olivier
authors.initials: O
authors.lastname: Diaz
authors.forename: Alexandre
authors.initials: A
authors.lastname: Deloire
authors.forename: Olga
authors.initials: O
authors.lastname: Azocar
authors.forename: Joël
authors.initials: J
authors.lastname: Baguet
authors.forename: Marc
authors.initials: M
authors.lastname: Le Breton
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Mangeot
authors.forename: Vincent
authors.initials: V
authors.lastname: Navratil
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Joubert
authors.forename: Monique
authors.initials: M
authors.lastname: Flacher
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Vidalain
authors.forename: Patrice
authors.initials: P
authors.lastname: André
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Martine
authors.initials: M
authors.lastname: Biard-Piechaczyk
authors.forename: Chantal
authors.initials: C
authors.lastname: Rabourdin-Combe
authors.forename: Mathias
authors.initials: M
authors.lastname: Faure
mesh_terms: D001343:Autophagy / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D019295:Computational Biology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D012327:RNA Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000635:transmission*; D012328:RNA Viruses / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins; D019204:GTP-Binding Proteins; C513539:IRGM protein, human