Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius

Stenglein, Mark D.; Jacobson, Elliott R.; Wozniak, Edward J.; Wellehan, James F. X.; Kincaid, Anne; Gordon, Marcus; Porter, Brian F.; Baumgartner, Wes; Stahl, Scott; Kelley, Karen; Towner, Jonathan S.; DeRisi, Joseph L.

In other nidoviruses, the replicase gene, comprised of ORF1a and ORF1b, encodes nonstructural proteins involved in viral genome replication and modulation of host cell activities (1-3, 9, 10, 29) . ORF1a is translated to produce the pp1a polyprotein. A fraction of translating ribosomes undergo a Ϫ1 frameshift near the end of ORF1a, resulting in the continuation of translation though ORF1b and the production of the pp1ab polyprotein. This virus is likely to utilize a similar mechanism of translation. ORF1a and ORF1b are offset by a Ϫ1 frame difference and overlap by 52 nt. This overlapping region contains a putative "slippery" sequence (AAAAAAC) that may be the site of frameshifting ( Fig. 4A ; see also Fig. S2 in the supplemental material) (35, 36) . In this virus, pp1a is predicted to be a 5,803-amino-acid (aa) protein with a molecular mass of 663 kDa, and pp1ab is predicted to be 8,108 residues long with a mass of 925 kDa (Fig. 4E) . As is the case for other nidoviruses, it is likely that these polyproteins are proteolytically cleaved into multiple functional domains (37) .