IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

PLoS Pathogens

Olga Azocar¹  Martine Biard-Piechaczyk¹  Clémence Richetta¹  Pierre-Olivier Vidalain¹  Fabrine Pradezynski¹  Vincent Navratil¹  Joël Baguet²  Olivier Diaz²  Chantal Rabourdin-Combe²  Laurène Meyniel-Schicklin²  Pierre-Emmanuel Joubert²  Patrice André²  Vincent Lotteau³  Mathias Faure³  Alexandre Deloire³  Sophie Borel³  Philippe E. Mangeot³  Monique Flacher³  Isabel Pombo Grégoire³  Marc Le Breton⁴ 

[1] INSERM, U851, Lyon, France;Université Lyon1, UMS3444/US8, Lyon, France;Université de Lyon, Lyon, France;Université de Montpellier, CPBS, UM1, UM2, CNRS, Montpellier, France

关键词: Autophagic cell death;    RNA viruses;    Protein interaction networks;    HIV-1;    Influenza;    Influenza A virus;    Protein interactions;    HeLa cells;   

DOI  :  10.1371/journal.ppat.1002422

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY