The Replication Strategy of SARS-CoV
(a) The severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) glycoprotein attaches to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. On entering the cytoplasm, the viral core particle, which contains the positive (5′ to 3′) strand genomic ribonucleic acid (RNA), is released into the cytoplasm of the cell (b). The positive-strand viral RNA is translated on host ribosomes to generate a large polyprotein (c) that undergoes proteolytic processing to generate multiple viral proteins, including an RNA-dependent RNA polymerase (RdRp). The RNA-dependent RNA polymerase generates a full-length, antisense negative-strand (3′ to 5′) viral RNA strand (d) that serves as template for replicating positive-strand viral genomic RNA, as well as shorter negative-strand RNAs (e) that serve as templates for synthesizing messenger ribonucleic acids (mRNAs) that code for structural proteins of the virus (f), including the S, membrane (M), envelope (E), and nucleocapsid (N) proteins. Translation of viral mRNAs occurs using the host endoplasmic reticulum (ER) (g). Once the viral structural proteins, S, E, and M, are translated and inserted into the ER, they move along the secretory pathway to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (h). The viral proteins become encapsulated and bud into membranes containing viral structural proteins, where mature virions are assembled. (i) Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis. Modified from Turner et al. (43). ORF = open reading frame.