Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease

Stenglein, Mark D.; Sanders, Chris; Kistler, Amy L.; Ruby, J. Graham; Franco, Jessica Y.; Reavill, Drury R.; Dunker, Freeland; DeRisi, Joseph L.

Two of the eight snakes diagnosed as IBD positive in this study tested negative for arenavirus infection (Table 1 ). There are a number of other possible causes of the pathology observed in these cases. One obvious alternative is infection by other viruses not detected by our methods, including additional divergent arenaviruses. A precedent for this possibility is the case of avian proventricular dilatation disease, where follow-up studies identified numerous additional genogroups of avian bornavirus, the causative agent (15, (51) (52) (53) (54) . Deep sequencing of additional IBDpositive samples will help resolve this question. Alternatively, infection by nonviral pathogens may be responsible in some cases, though we did not detect any obvious such organisms in our metagenomic analyses. Alternatively, the cytoplasmic inclusions may be a by-product of some other disease state or cellular stress, although the localization of viral nucleoprotein to these inclusions that we observed would appear to contradict this alternate hypothesis. Expanded association studies will more firmly determine the proportion of IBD cases attributable to arenavirus infection and may identify etiologic agents responsible for nonarenavirus IBD diagnoses.