IRGM is a common target of RNA viruses that subvert the autophagy network

• Published in: PLoS pathogens Vol. 7; no. 12; p. e1002422
• Main Authors: Grégoire, Isabel Pombo, Richetta, Clémence, Meyniel-Schicklin, Laurène, Borel, Sophie, Pradezynski, Fabrine, Diaz, Olivier, Deloire, Alexandre, Azocar, Olga, Baguet, Joël, Le Breton, Marc, Mangeot, Philippe E, Navratil, Vincent, Joubert, Pierre-Emmanuel, Flacher, Monique, Vidalain, Pierre-Olivier, André, Patrice, Lotteau, Vincent, Biard-Piechaczyk, Martine, Rabourdin-Combe, Chantal, Faure, Mathias
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-12-2011; Public Library of Science (PLoS)
• Subjects: Autophagy; Autophagy (Cytology); Autophagy - physiology; Base Sequence; Biology; Blotting, Western; Cellular Biology; Cloning; Computational Biology; Defense mechanisms; Genes; Genetic aspects; GTP-Binding Proteins; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Guanosine triphosphatase; Health aspects; HeLa Cells; HIV; Human health and pathology; Human immunodeficiency virus; Humans; Infectious diseases; Influenza; Life Sciences; Measles; Microbiology and Parasitology; Microscopy, Confocal; Mitochondria; Molecular Sequence Data; Names; Open Reading Frames; Open Reading Frames - genetics; Physiological aspects; Proteins; RNA Virus Infections; RNA Virus Infections - genetics; RNA Virus Infections - metabolism; RNA Virus Infections - transmission; RNA Viruses; RNA Viruses - genetics; RNA Viruses - metabolism; RNA, Small Interfering; Transfection; Two-Hybrid System Techniques; Viral Proteins; Viral Proteins - metabolism; Virology; Viruses; Yeast; France
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002422

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.