Hosting the severe acute respiratory syndrome coronavirus: specific cell factors required for infection

Abstract

As with all viruses, the severe acute respiratory syndrome coronavirus (SARS-CoV) utilizes specific host cell factors during its infection cycle. Some of these factors have been identified and are now increasingly scrutinized as targets to intervene with infection. In this brief review, we describe the current understanding of how the SARS-CoV is able to use the cellular machinery for its replication.

Figure 1

SARS‐CoV life cycle. The infection cycle of the SARS‐CoV starts with the binding of the virion to the receptor ACE2. After endocytosis, the S protein is cleaved by cathepsin L (represented by the scissors), after which the viral envelope fuses with the host cell membrane. Next, the virus disassembles, releasing its genomic RNA into the cytoplasm of the host cell. Translation of the replicase genes produces two large precursor proteins (pp1a and pp1ab) the many cleavage products of which (nsp1‐16) collectively constitute the functional replication–transcription complexes on double‐membraned vesicles (DMVs). Genes located downstream of the replicase genes are expressed from a 3′‐coterminal nested set of subgenomic mRNAs, each of which contains a short 5′ leader sequence derived from the 5′ end of the genome (shown in red). Many copies of N protein package the genomic RNA into a helical nucleocapsid. The envelope proteins (S, 3a, E and M) are inserted into the ER membrane, and accumulate in the ER‐to‐Golgi intermediate compartment (ERGIC) to meet the nucleocapsid and, subsequently, to assemble into particles by budding. Finally, the complete virions are transported out of the cell via the constitutive secretory pathway.