FIG. 1.
MHV genome organization, proteolytic processing of the replicase polyproteins, and putative cleavage sites of nsp7 to nsp10. (A) The 5′ two-thirds of the MHV genome encode the ORF1 replicase proteins pp1a and pp1ab. ORF2 to ORF7 encode the major structural proteins S, E, M, and N, along with several accessory proteins. (B) The replicase polyproteins are processed by three proteases to produce 16 mature proteins. PLP1 is responsible for cleaving between nsp1-nsp2 and nsp2-nsp3 (black arrows), while PLP2 cleaves between nsp3-nsp4 (open circle). Mpro processes the remainder of the polyproteins (open triangles). The replicase proteins include a number of functionally conserved domains, including the two PLP proteases, an ADP-ribose-1‴-monophosphate-processing enzyme (X), three hydrophobic transmembrane domains (TM, MP1, and MP2), the nsp5 protease (Mpro), RdRp, a putative zinc-binding domain (Z) and helicase (Hel), an exonuclease (ExoN), an endoribonuclease (EU), and an S-adenosylmethionine-dependent ribose 2′-O-methyltransferase (OMT). (C) The amino acid sequences of the Mpro cleavage sites falling within the nsp7 to nsp10 region of the replicase polyproteins are shown (open arrows denote points of cleavage) along with their P1 Gln amino acid positions. A second putative cleavage site falling between nsp7-nsp8 is identified with a question mark and a vertical dotted line illustrating its proposed cleavage site.