When the folks at the Steinhart Aquarium in San Francisco were confronted with an outbreak of the mysterious condition called Inclusion Body Disease (IBD) among their boa constrictors and pythons, they knew they needed help.
Or, in this case, a team of microbiologists. In mBio this week, Stenglein et al. report that they may well have found the virus responsible for this common but deadly disease, a discovery that could eventually lead to prevention and treatment options. The virus represents a whole new class of arenaviruses that's never been seen before.
Among captive boas, IBD is the most commonly diagnosed disease that is thought be caused by a virus. Snakes that have contracted IBD may initially regurgitate food, but they eventually show dramatic neurological problems, says Michael Buchmeier, a professor of infectious diseases at the University of California, Irvine, who edited the paper. Neurological signs include "stargazing", in which the snake stares upwards for long periods of time.
"Some of the symptoms are pretty bizarre - this stargazing behavior, looking like they're drunk, they tie themselves in a knot and they can't get out of it," says Buchmeier. The condition, which is named for the inclusions, or pockets of foreign material, found inside the cells of affected animals, is ultimately fatal. IBD is devastating for large aquariums, as it can infect a large number of snakes before it is identified and quarantine measures can be put in place. Since there is currently no treatment for the disease, infected snakes must be euthanized to prevent them from infecting other animals.
When the disease recently struck boas and pythons at the Steinhart Aquarium at the California Academy of Sciences, the aquarium requested help from Joe DeRisi's lab at the University of California San Francisco. DeRisi and his lab specialize in discovering novel viruses. (Listen to my interview with DeRisi from a couple years ago here.)
Using tissue samples taken from boas and pythons diagnosed with IBD, they extracted the RNA and used high-throughput sequencing to try and find the proverbial viral needle in the haystack. After removing the boa sequences* and the low quality sequences, they subjected the remaining sequences to BLAST analyses and assembled them. They ultimately came up with the full genome sequences of two related viruses, both of which have characteristic attributes of arenaviruses but also share some sequence similarity with filoviruses . They were later able to grow and isolate one of those viruses using snake tissues cultured in the laboratory.
It's an important development from a practical standpoint, since identifying the causative agent for a disease is the first step in developing treatments, vaccines, diagnostics, and prevention policies. But it's also an incredible discovery for virology: the virus belongs to a group of arenaviruses no one knew existed.
"This is one of the most exciting things that has happened to us in virology in a very long time. The fact that we have apparently identified a whole new lineage of arenaviruses that may predate the New and Old world is very exciting," says Buchmeier.
According to Buchmeier, this new isolate doesn't fall neatly into either of the two known categories of arenaviruses, Old World arenaviruses and New World arenaviruses. The fact that the virus was found in snakes adds another surprise twist, since up until now arenaviruses had only ever been found in mammals.
Metagenomic techniques that examine large samples of DNA for small bits of information, like the approach used in the study, are extremely powerful for identifying new viruses, Buchmeier says.
"Twenty years ago we would have called this a fishing expedition. It is fishing, but the techniques are so good and so sensitive that they allow us to determine which new types are there," says Buchmeier.
*They actually sequenced the boa genome for this purpose. Sequencing the genome of an animal is now apparently a minor step on your way to getting to the actual data. Hardly even worthy of a footnote. But here it is anyway.