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 this report, we describe a severe respiratory disease affecting ball pythons, and we have identified a nidovirus as a candidate etiologic agent by means of association. We collected cases from around the United States and performed a variety of pathological and diagnostic analyses. Respiratory tract pathology was consistent with a viral etiology, as was the presence of virus-like particles in lung epithelium of affected snakes. Using unbiased deep sequencing, we identified and assembled the genome of a previously uncharacterized nidovirus. This virus shares several attributes with other nidoviruses but has several distinguishing characteristics, including its record-setting genome size and reptile host. The findings presented here raise a number of questions related to the biology of this virus and its relationship to disease. Foremost among these is whether this virus causes the observed respiratory pathology. Several observations suggest a causal relationship. First, detection of viral RNA correlates with clinical signs. Second, the virus load is most profound in the respiratory tract, the site of disease. Third, other animal nidoviruses cause severe respiratory disease. Nevertheless, formal evidence of disease causality remains to be demonstrated. Although virus isolation attempts have yet to succeed, experimental infections using material prepared directly from infected tissues could fulfill Koch's postulates.