Figure 2. Life cycle of coronaviruses and implications for translation regulation.

Numbers (1–9) indicate life cycle steps of the virus, while interactions with host translation are represented by letters (A–H). Upon binding of a virion to host receptors, membrane fusion releases the positive sense RNA genome into the cytoplasm (1). The genome is translated by the host cell machinery to produce two different polyproteins by programmed ribosomal frameshifting (2 and A). Cleavage of polypeptides (3) produces non-structural proteins (Nsps), including RdRp that synthesize negative and positive sense (−Sense and +Sense) RNAs (4, 5) inside of double-membrane vesicles (DMV) that act as platforms for viral replication. Nsp1 binds to ribosomes (B), inhibits host mRNA translation and stimulates host mRNA degradation (C). Viral RNAs are polyadenylated, and when their concentration is increased, they compete to bind Poly(A)-binding proteins (PABP) (D). RNA editing (E) may introduce variable sequences in the viral progeny and alter the translation and stability properties of the viral RNAs. The subgenomic RNAs are translated to synthesize structural and accessory proteins (6 and F) that can stimulate stress responses (G) in the ER. PKR and PKR-like endoplasmic reticulum kinase (PERK) activation triggers eIF2α phosphorylation that, in turn, inhibits cap-dependent translation (H). The nucleocapsid buds into the ER–Golgi intermediate compartment (ERGIC), which is covered by the structural proteins S (spike), E (envelope), and M (membrane) (7). Exocytosis (8 and 9) exports the virion from the cell.