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.

Unbiased, high-throughput methods are transforming the ability to identify candidate etiologic agents in infectious diseases of unknown cause (11) (12) (13) . Metagenomic pathogen discovery techniques aim to identify pathogen nucleic acid in infected samples without bias. The first generation of such technologies included the Virochip microarray (14, 15) . Now, high-throughput sequencing, such as the Illumina technology, is being increasingly used as its price decreases and throughput increases. The massive depth of sequence combined with increasingly capable assembly and search methods offers greater sensitivity to detect divergent pathogens than ever before. Ultimately, however, sequencing can only ever identify candidate etiologic agents, and demonstration of causality requires significant additional experimental effort.