Figure 3

A model of the life cycle of reovirus: proposed checkpoints based on function of the cellular genes identified by the insertional mutagenesis The virus life cycle begins (top, clockwise) with virus binding to cell surface receptor and being endocytosed into early endosomes. These endosomes then associate with annexin-II (Anxa2) [62] and fuse with annexin-II-associated vesicles containing newly synthesized lysosomal enzymes migrating from the Golgi [63], which further fuse with the lysosome. The vacuolar H⁺-ATPase (Atp6v0c) acidifies the lysosome, allowing acid-dependent proteases to digest the outer coat from the virus particles and activate them [64]. These activated particles then pass through the lysosomal membrane and begin transcription of mRNA. The Golgi protein gm 130 (Golga2) is believed to mediate the docking of vesicles as they carry their newly synthesized cargo through the Golgi stack [65, 66]. N-acetylglucosaminyl transferase I (Mgat1) initiates the glycosylation of cell surface proteins (receptors?) and may play a major role, through kinship recognition, in helping maintain the correct assortment of lysosomal enzymes [67-71]. The Igf2r shuttles enzymes bound for the lysosome from the Golgi [72] and transfer Igf2 to the lysosome. While the roles of calcyclin and the α-tropomyosin (Tpm1) are still unclear, they specifically bind each other, and calcyclin is known to bind Anxa2 [16, 20]. Thus, they may be involved in endosome fusion. Eif3s10 specifically binds the virus message to begin its preferential translation. The DnaJa1 protein may facilitate the proper folding of virus proteins with its chaperone function [73]. However, DnaJa1 protein and Eif3 may play additional roles in virus trafficking or apoptosis, respectively. Eventually, morphogenesis is complete when crystalline-like arrays of new virions form, cell lysis occurs, and virus is released. Many of the cellular proteins encoded by mutated genes have direct or indirect roles in trafficking of endosomes or lysosomal fusion and thus may play roles in the early disassembly or delivery of transcriptionally active virions to the appropriate cell location.