Genome organization and polyprotein products of human astrovirus. (A) Genomic and subgenomic RNA organization, with open reading frames (ORFs) ORF1a, ORF1b, ORF2, and putative ORFX represented as boxes. Nucleotide sequences represent highly conserved sequences located in the ribosomal frameshift (RFS) signal and upstream of the initiation site of subgenomic RNA transcription. Putative RNA secondary structures conserved in the RFS and in the 3′ end of the genome are depicted. (B) Characteristic motifs of the HAstV polyprotein products. HEL, putative helicase domain; TM, transmembrane domain; CC, coiled-coil domain; PRO, protease domain; VPg, coding region for a VPg protein; HVR, hypervariable region; NLS, putative nuclear localization signal; DD, putative death domain; RdRp, RNA dependent-RNA polymerase motif. The ORF2-encoded structural polyprotein (VP90) consists of conserved regions (shell and P1 domains), a variable region containing the P2 domain (capsid spikes), and an acidic C-terminal region which is cleaved by cellular caspases to result in the VP70 precursor. Particles containing VP70 are further cleaved by trypsin to yield the VP34, VP27/29, and VP25/26 proteins.