IRGM in autophagy and viral infections

Denitsa S. Petkova, Christophe Viret, Mathias Faure

Autophagy is a cell autonomous process allowing each individual cell to fight intracellular pathogens. Autophagy can destroy pathogens within the cytosol, and can elicit innate and adaptive immune responses against microorganisms. Nevertheless, numerous pathogens have developed molecular strategies enabling them to avoid or even exploit autophagy for their own benefit. IRGM (immunity-related GTPase family M) is a human protein recently highlighted for its contribution to autophagy upon infections. The physical association of IRGM with mitochondria and different autophagy-regulating proteins, ATG5, ATG10, SH3GLB1, and LC3, contribute to explain how IRGM could regulate autophagy. Whereas IRGM is involved in autophagy-mediated immunity against bacteria, certain viruses seem to have developed strategies to manipulate autophagy through the selective targeting of this protein. Furthermore, irgm variants are linked to infection-associated human pathologies such as the inflammatory Crohn's disease. Here, we discuss how IRGM might contribute to human autophagy upon viral infection, and why its targeting might be beneficial to virus replication.