Metatranscriptomic sequencing approaches reveal the identity of an equine serum hepatitis: Theiler disease

Metatranscriptomic sequencing approaches reveal the identity of an equine serum hepatitis: Theiler disease

In an article entitled, “Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis,” published in March 18, 2013, issue of PNAS (, the lead author Sanjay Chandriani with seven other associates from two research groups have identified a previously unknown virus as a potential cause of Theiler disease, an acute form of equine hepatitis of horses with mortality rates up to 90%. For nearly a century, the cause of Theiler disease has remained a mystery. The disease, which can trigger lethargy, anorexia, elevated blood levels of liver enzymes, jaundice, fever, blindness, and coma. Donald Ganem and colleagues used a high-throughput DNA sequencing method and phylogenetic analysis to uncover a potential causal agent for Theiler disease during an outbreak on a horse farm. They searched among the more than 60 million resulting reads from these samples for foreign, nonhorse sequences with similarity to viruses. Their analysis identified a 10.5-kb sequence from a previously unknown and highly divergent virus of the Flaviviridae family (which includes human hepatitis C virus and yellow fever virus) that they designate Theiler’s disease associated virus (TDAV). Further, an epidemiological survey in three independent locations revealed that eight of the 17 horses treated with an antitoxin preparation containing the virus, named Theiler disease-associated virus (TDAV), developed hepatitis, suggesting that TDAV might be a causal agent of the disease. Although the study does not conclusively establish TDAV as the cause of Theiler disease, it provides an epidemiological link between the virus and the disease, according to the authors. This study provides a compelling example of how the combination of unbiased metatranscriptomic sequencing approaches and classical epidemiology can elucidate the role of previously unknown viral agents in diseases of unknown etiology. This study also presents opportunities to investigate a potentially important pathogen of horses and provides critical information for efforts directed toward the control and eradication of this dangerous equine serum hepatitis. [Summarized by Samsad, a graduate student in the Plant Biotech Lab, DU]

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