Following entry and uncoating, the 5′ most replicase gene of the input positive strand RNA genome is translated into two co-amino terminal replicase polyproteins that are co- and post-translationally processed by viral proteinases to yield 15 to 16 mature replicase proteins, as well as intermediate precursors. The nascent replicase polyproteins and intermediate precursors likely mediate the formation of viral replication complexes in the host cell cytoplasm. Interestingly, coronavirus replication requires continuous replicase gene translation and processing throughout the life cycle to maintain productive infection (Kim et al., 1995; Perlman et al., 1987; Sawicki and Sawicki, 1986). Replication complexes of MHV are associated with double-membrane vesicles (Gosert et al., 2002), and all tested MHV replicase proteins have been shown to colocalize to replication complexes at the earliest time of detection, likely both by membrane integration and by protein-protein and protein-RNA interactions (Bost et al., 2000; Denison et al., 1999; Prentice and Denison, in press; Shi et al., 1999; Sims et al., 2000; van der Meer et al., 1999). Further, replicase proteins likely mediate the process of double-membrane vesicle formation, likely by induction of cellular autophagy pathways (E. Prentice, unpublished results).
Coronavirus replication complexes are sites for replicase gene translation and replicase polyprotein processing, and also for viral RNA synthesis. Replicase gene proteins likely mediate positive-strand, negative-strand, subgenomic, and genomic RNA synthesis, as well as processes of capping, polyadenylation, RNA unwinding, template switching during viral RNA synthesis, and discontinuous transcription and transcription attenuation. The coronavirus replicase polyproteins and mature replicase proteins represent the largest and most diverse repertoire of known and predicted distinct enzymatic functions of any positive-strand RNA virus family. Until recently, of the 15 or more mature replicase proteins, only the proteinase, RNA helicase, and RNA-dependent RNA polymerase activities had been predicted or experimentally confirmed (Brockway et al., 2003; Heusipp et al., 1997; Lee et al., 1991; Ziebuhr et al., 2000). With the advent of SARS, more extensive bioinformatics analyses have resulted in predictions of several additional functions involved in RNA processing, including methyltransferase and exonuclease activities (Snijder et al., 2003; Thiel et al., 2003). Even with inclusion of distant predicted relationships, up to eight of the replicase proteins remain without predicted or confirmed functions. In summary, it is likely that coronaviruses have exploited their genetic capacity to encode proteins in the replicase gene with distinct functions in RNA synthesis and processing, as well as proteins with specific roles in induction or modification in host cellular membrane biogenesis and trafficking, delivery of replication products to sites of assembly, and possibly virus assembly. Thus replicase translation, replicase polyprotein processing, and mature replicase proteins constitute important targets for interference with coronavirus replication, virus-cell interactions, or viral pathology.
Ref and Source : https://www.ncbi.nlm.nih.gov/books/NBK92477/