Reovirus Life Cycle. ReoV enters cells (Step 1) following binding of σ1 protein to host cell receptor, such as JAM-A and, in some cases, sialic acids. Clathrin-mediated endocytosis is the most common entry mechanism, although caveolin-mediated endocytosis and macropinocytosis is also possible. The virions are then shuttled within endosomes. Proteolysis degrades the outer σ3 protein and cleavage of the unveiled µ1C into fragments δ and φ, leading to formation of the ISVP. The µ1C cleavage fragments, along with µ1N, form pores within the endosomal membrane, depositing the viral core now lacking both µ 1 and σ1. Transcription by the RdRp λ3 occurs within the viral core underneath channels formed by λ2 (Step 2). Capping of mRNA is mediated by λ2. Viral mRNA is exported from the viral core and into the cytoplasm, where translation occurs (Step 3). Viral proteins mediate nucleation of viral factories, where progeny cores begin to self-assemble (Step 4). Negative strand synthesis occurs within progeny cores, forming nascent viral genomes (Step 5). Progeny core transcription occurs, and outer capsid proteins begin to assemble around progeny cores (Step 6). Finally, progeny virons leave the cell, either via lytic or non-lytic egress (Step 7).