Downstream of the PK there is a hypervariable region (HVR) that is highly divergent in sequence and structure among coronaviruses but contains a universally conserved octanucleotide sequence in a single-stranded region. In MHV, the HVR was predicted to fold in a complex multiple stem-loop structure, which is nonessential for RNA synthesis in cell culture but affects pathogenicity in vivo. Although the strict conservation of the octanucleotide sequence suggests an important functional role, the activity of this sequence remains to be determined. Finally, MHV and BCoV defective interfering RNA studies have provided evidence that the poly(A) tail is another cis-replication signal that requires a minimum of 5 to 10 adenylate residues to be functional, probably via interaction with PAPB.