Fig. 1.

CoV replicase genes encode a putative ExoN. (A) Functional ORFs in the SARS-CoV genome are expressed from both genomic RNA and a set of eight sg mRNAs (17). ORFs encoding the four major structural proteins, S, E, M, and N, are shown in black. The ORF1a- and ORF1b-encoded proteins, pp1a and pp1ab, are cleaved by viral proteases to yield 16 processing end products called nsp1–16. The N-terminal part of nsp14 was predicted to harbor an ExoN domain (13). (B) Partial sequence alignment of representative CoV ExoN domains. ExoN residues (pp1ab numbering) that were targeted in this study by site-directed mutagenesis are indicated for SARS-CoV (denoted in bold type) and HCoV-229E (given in brackets). Also shown are the conserved exonuclease sequence motifs I–III (18).