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.

We next used the HMMER3 sequence analysis tool (http:// hmmer.org) to search the PFam database for particular pp1ab domains, and for the most part, these domains were present and organized as expected given the overall similarity to bafinivirus replicase polyproteins ( Fig. 4E and Table 2 ; see also Fig. S3 in the supplemental material) (1, 9, 32, 41, 42) . The expected domains present in snake virus pp1ab included a 3C-like protease located between two predicted transmembrane regions near the end of pp1a (TM2-M pro -TM-3), an RNA-dependent RNA polymerase (RdRp), a helicase (Zn-Hel), a 3= to 5= exoribonuclease (ExoN), a nidoviral uridylate-specific endoribunuclease (NendoU), and a ribose-2=-O-methyltransferase found at the carboxy terminus of pp1ab (O-MT) ( Fig. 4E and Table 2 ) (12, 37, 38, 43, 44) . The replicase polyproteins of some taxa of nidoviruses encode a guanine-N7-methyltransferase (1, 9, 43, 45) . As is the case for viruses in the Torovirinae subfamily, snake virus pp1ab appears to lack this enzyme. Functional experiments will be necessary to validate the cleavage patterns, biochemical activities, and roles in the virus life cycle of these predicted replicase proteins.