Polar bear Knut with his zookeeper Thomas Doerflein (who had died in 2008) on the day of the first public appearance of the little bear in March 2007.

The culprit of the sudden death of famed polar bear tot Knut has been found, says an international team of scientists. An exhaustive analysis shows a viral form of encephalitis, or brain swelling, led to the seizures and untimely death.

"After a detailed necropsy and histology that took several intense days to perform, the results clearly suggested that the underlying cause of Knut's seizures was a result of encephalitis, most likely of viral origin," Claudia Szentiks, of the Leibniz Institute for Zoo and Wildlife Research Berlin (IZW), said in a statement.

Born in captivity at the Berlin Zoo on Dec. 5, 2006, Knut quickly rose to celebrity-hood after he was rejected by his mama and hand-raised by Thomas Dorflein, a zookeeper who died in 2008 of a heart attack. [See Photos of Polar Bear Knut's Life]

Then on March 19, 2011, the 4-year-old bear died suddenly in front of hundreds of zoo visitors.

"There was absolutely nothing to see. I was there one hour before he died, and I saw him resting there and he recognized me and he was absolutely normal in his behavior," said Heiner Klös, bear curator and biologist at the Berlin Zoo, at the time.

Knut's death

Preliminary results from a necropsy, or animal autopsy, just after his death showed brain abnormalities though no evidence of irregularities of Knut's organs. "We are absolutely sure there was no stress and no heart attack, and no broken heart, if it's possible to find something like this," Klös, who was responsible for Knut's care, told LiveScience in 2011.

Even so, Knut's death at such a young age is rare; male polar bears in zoos typically live into their mid-30s, whereas those in the wild survive between 15 and 18 years, according to the San Diego Zoo. [In Photos: Zoo Babies Born in 2013]

Now, in the most exhaustive investigation into cause of death, including an extensive look at gene sequences from Knut to see if any matched up with known pathogens, researchers say a viral encephalitis is likely the culprit.

"Because of the seizures previous to his death we were already expecting that there was something wrong within the central nervous system," Szentiks told LiveScience in an email. "But as there were no signs of disease beforehand there was no clinical checkup. And therefore nobody could have known for sure before the histology that there was an inflammation."

This brain-inflammation disease can be caused by several pathogens. For instance, equine herpesviruses known to have killed a female polar bear at Wuppertal Zoo in Germany in 2010 can cause encephalitis. (Knut's father Lars survived an infection with equine herpesviruses.)

The team found no evidence of equine herpesviruses, though they did find antibodies for the influenza A virus in Knut's blood; antibodies are proteins TK and suggest in this case Knut had been exposed to the flu virus, though researchers say it is unlikely to have been the cause of death since evidence of the virus wasn't found in Knut's brain.

"After so much hard work, the results appear ultimately sobering," Klaus Osterrieder, chair for veterinary virology at the Freie Universität Berlin, said in a statement. "We cannot and therefore should not blame influenza as the source of death."

Novel virus?

So what was behind Knut's brain inflammation and death? "There are two possibilities now," Szentiks wrote. "Either Knut suffered from an infection and the agent was eliminated, or the virus belongs to a new group of viruses which are unknown. And therefore for that virus family there are no known sequences, which are needed to identify it."

If there is any upside to Knut's death, it is perhaps the knowledge that has come out of examining the bear.

"Studying Knut and his relatives has revealed that equine herpesviruses from zebras and possibly other equids have turned out to be a serious problems in zoos," said Alex Greenwood, head of the department of wildlife diseases at the Leibniz Institute for Zoo and Wildlife Research Berlin. He and colleagues just published a scientific paper describing encephalitis in both a polar bear and an Asian rhino, the latter fatally infected, Greenwood told LiveScience.

In addition, "because of the new knowledge on pathogens in polar bears the zoos can now begin to develop management strategies to minimize their occurrence," Heribert Hofer, head of the IZW, said in a statement.

The new research involved scientists from the Leibniz Institute for Zoo and Wildlife Research Berlin (IZW), the Freie Universität Berlin, the Friedrich Loeffler Institute – Insel Riems, the Max Delbrück Center for Molecular Medicine in Berlin, the University of California at San Francisco and many others.

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