Orchestrated efforts on host network hijacking: Processes governing virus replication

Dai, Xiaofeng; Hakizimana, Olivier; Zhang, Xuanhao; Kaushik, Aman Chandra; Zhang, Jianying

Autophagy can be schematically divided into phagophore initiation, elongation, and fusion with lysosomes, which are executed by different autophagy-related (Atg) genes. In mammals, the unc-51 like autophagy activating kinase 1 (ULK1) complex, autophagy-related protein 13 (ATG13), FAK family kinase-interacting protein of 200 kDa (FIP200), and ATG101 are recruited either on cellular membranes at the ER-mitochondrial junction [16] or at the ER-Golgi intermediate compartment [17] during the initiation phase in a manner strictly regulated by nutrient conditions through mTOR (the mammalian target of rapamycin) [18] . The phagophore is produced by sequential recruitment of autophagy factors and membranes, which facilitates the formation of the curved double-membrane sheet that detaches from the membrane where it originates from. The class III phosphatidylinositol 3 kinase (PI3K) complex contains VPS34, Beclin 1 (ATG6), VPS15, ATG14L or UVRAG (UV radiation resistance-associated gene protein), where the regulatory subunits Beclin 1, VPS15, and ATG14L mediate phagophore membrane expansion during the elongation process. The class III PI3K complex is activated by Beclin 1 dissociation, resulting in the recruitment of PE (phosphatidylethanolamine) and LC3 (microtubule-associated protein 1 light chain 3) that promote the conjugation of lipid molecules [19] . Finally, the class III PI3K complex II which consists of VPS34, VPS15, Beclin 1, and UVRAG is activated to induce the GTPase activity of Rab7 (Rasassociated protein-7) that leads to autophagosome fusion with late lysosomes [20] .