Unusual virus may tie snakes in knots

Newly discovered class could be the cause of fatal disease

A newly discovered class of virus may be at fault in a disease that causes snakes to regurgitate their food, stop eating, and even twist themselves into knots.

Researchers deciphered the complete genetic makeup of a healthy boa constrictor named Balthazar (pictured) and used the information to identify the virus that may cause a deadly snake disease. Joseph DeRisi

Large clumps of proteins (green) are the hallmark of an infection in snakes called inclusion body disease. Researchers may have pinpointed the virus that causes the fatal illness. Mark Stenglein

Researchers at the University of California, San Francisco, found three new viruses in captive snakes with inclusion body disease, a fatal illness that strikes boa constrictors and pythons and causes clumps of proteins to build up in the snakes’ cells. The unusual genetic makeup of the viruses could give scientists clues to virus evolution stretching back to the age of the dinosaurs.

“It is so different from anything out there it’s almost unrecognizable. It’s way out there,” says Joseph DeRisi, a Howard Hughes Medical Institute investigator at UCSF who led the work, which appears online August 14 in mBio.

The newly identified viruses are similar to arenaviruses, a class previously found only in rodents. Sometimes an arenavirus, such as the one that causes Lassa hemorrhagic fever, will infect a human, but the viruses have never been found in reptiles before.  

But the snake viruses have a feature not seen in any arenavirus — a gene found in Ebola, which is in a completely different class called filoviruses. Virologists never thought it possible that those two classes could swap genes, says William Gallaher, a virologist and emeritus professor at Louisiana State University Health Sciences Center in New Orleans.

Ebola could have mixed with arenaviruses long ago, resulting in the combination snake virus. But Gallaher thinks the possibility is slim. The two virus types have different biology, so finding them both active in the same cell at the same time to mix their genetic material seems unlikely, he says.

DeRisi is excited about another possibility: Perhaps the snake viruses are an ancient ancestor to the arenaviruses and filoviruses. “Maybe what you’re looking at is a dinosaur virus eons old,” he says. The ancient reptile viruses may then have given rise to arenaviruses that infect rodents.

Or it could be the other way around: The newly discovered viruses may have originally infected rodents, as arenaviruses do today. Sometime in the murky past, a rodent may have passed its virus on to the snake that ate it, says coauthor Mark Stenglein, a virologist working in DeRisi’s lab. “We call that the rodent revenge hypothesis.”

There is no evidence that modern mice are passing the disease to pet snakes, Stenglein says. And although the viruses were found in snakes with inclusion body disease, that doesn’t necessarily mean the virus causes the illness. The next step will be to infect healthy snakes with the viruses to see if they develop the disease.

The snake viruses are so different that they are probably in a class by themselves, DeRisi says. An international board of experts on viral taxonomy will have the final say over whether the viruses are really a new class, but DeRisi is confident they are distinct. “It’s kind of a no-brainer,” he says.

Back Story | The snake lady’s letter

Joseph DeRisi wasn’t sure at first what to make of the letter he got a few years ago from Taryn Hook of San Jose, Calif., not to mention the photo she enclosed of herself with a boa constrictor draped around her neck. It wasn’t the sort of thing the UCSF virologist is accustomed to finding in his mail.

Hook’s letter explained that she was worried her beloved 15-year-old boa constrictor, Larry, had contracted inclusion body disease, a mystery illness that had already claimed the lives of her two other pet snakes.

Hook’s letter noted that inclusion body disease can cause bizarre behavior and digestive problems — Larry once refused to eat for six months — and that the virus causing the condition was unknown. Since DeRisi had previously identified viruses that cause a mysterious disease in parrots called proventricular dilatation disease, Hook suggested, perhaps he could help.

DeRisi confesses that the letter and photo sat on his desk for a while. He was about to toss them, but something stopped him. “It was the veterinarian’s phone number at the bottom of the letter that clued me in that this thing might be real.” He called Larry’s vet, Chris Sanders of Wildwood Veterinary Hospital in Portola Valley, Calif., and was soon convinced that inclusion body disease was worth going after. Several years of research have now led to the discovery of three previously unknown viruses that may be linked to the disease.

Larry, the snake who started it all, has tested negative for all three of the viruses. What’s ailing him remains a mystery.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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