Figure 1.

Autophagy machinery and its modulation by viruses. Beclin-1/PI3KC3 complex activation, which is regulated by different mechanisms including the ULK1/2 complex and mTORC1 complex, results in the induction of an autophagic vesicle, which is characterized by a double-membrane, named autophagosome. Two ubiquitin-like systems are essential for autophagosome formation. In the first, autophagy-related gene-12 (Atg12) is conjugated to Atg5, together forming a complex with Atg16L1, which decorates the outer membrane of the phagophore. Microtubule-associated protein 1 light chain-3 (LC3, also known as Atg8) constitutes the second ubiquitin-like system and conjugates phosphatidylethanolamine (PE) at the outer and inner autophagosomal membrane. Unlike the Atg12/Atg5/Atg16L1 complex that is recycled by the protease Atg4, the LC3-PE (referred to LC3-II) remains associated with the inner membrane of autophagosome. The incorporation of phospholipid into the autophagosome membrane is essential for its elongation and regulates the membrane transport system. Autophagosome maturation is characterized by the formation of an autolysosome, the product of fusion with the lysosome. Viruses activate or inhibit autophagy at several step, as indicated on the figure. VSV, Vesical Stomatitis Virus; SeV, Sendai Virus; MeV, Measles Virus; HIV, Human Immunodeficiency Virus; CRads, Conditionally Replicating Adenoviruses; HSV, Herpes Simplex Virus; KSHV, Kaposi’s Sarcoma-associated Herpesvirus; MHV, Mouse Hepatitis Virus; HCMV, Human Cytomegalovirus; MCPyV, Merkel Cell Polyomavirus; HPV-16, Human Papillomavirus 16; EBV, Epstein-Barr Virus; HTLV-1, Human T cell Leukemia/lymphoma Virus type 1; CHIKV, Chikungunya Virus; HCV, Hepatitis C Virus; NDV, Newcastle Disease Virus; Polio, Poliovirus; IAV, Influenza A Virus; CVB3, Coxsackievirus B3; FMDV, Foot and Mouth Disease Virus; HPIV3, Human Parainfluenza Virus 3; HBV, Hepatitis B Virus.