New Virus Killer at the Zoo

When a 12-year-old polar bear at the San Diego Zoo died of unknown causes a year ago last July, a team of investigators, led by Dr. Mark D. Schrenzel of the zoo’s Center of Research for Endangered Species, was quickly called into the case.

A veterinary pathologist who has a degree in veterinary medicine and a Ph.D. in comparative pathology, Schrenzel heads the center’s molecular diagnostics laboratory at the San Diego Wild Animal Park, where the DNA of a mysterious virus found in tissue samples of the dead polar bear was minutely analyzed using cloning and sequencing techniques available at only a few veterinary labs in the world.

What Schrenzel and his team discovered was big news to scientists: a little-understood variation of a herpes virus common in Grevy’s zebras and other horse-related animals had somehow found its way into the polar bear and killed it. The so-called cross-species infection had ramifications far beyond the cloistered world of zoos; it indicated that such equine viruses might possibly have the potential to infect and kill human beings.

Schrenzel’s findings were so significant that they were published in the October issue of the journal Emerging Infectious Diseases, published by the federal Centers for Disease Control and Prevention in Atlanta, the government’s first line of defense against international contagions. In the paper, Schrenzel outlined his research results, calling out the need for further investigation. During a recent telephone interview, he recounted the history leading up to his discovery and its potential long-term ramifications for public health:

Clinically the polar bear became ill and received veterinary care for, I think, about a week. But his illness, despite therapy, progressed. So he was humanely euthanized.

Every animal that dies in our collection, or any animal from the wild that dies within the parameters of the San Diego Zoo or Wild Animal Park, receives a complete postmortem evaluation to assess them for possible diseases they may have had or may have been carrying as a way of — so we can know what’s going on to protect animals in our collection and also to know what’s going on in the adjacent wildlife.

We knew what type of lesions the polar bear had within a few days, and it had encephalitis that was suggestive of a viral infection. We started to add some ancillary diagnostic evaluations to see if we could determine which virus it was. So we tested it for a variety of different viruses, and we found that it was infected with a herpes virus, and that’s how we discovered this virus.

Our laboratory is designed to use innovative techniques and research to discover new pathogens in animals, so we use basic principles in molecular biology and apply them in a creative way to discover agents that haven’t been previously described. And this was a case of a virus that had not been recognized before here in San Diego.

It was totally — well, it had been previously described in other zoological institutes, but for us, it was the first time we had seen it in a non-equid. Part of our mission here is to ensure animal health and well-being by surveilling them for possible pathogens, and we had been studying the equids in our collection, which includes zebras, and onagers, kiangs, and Somali wild asses.

We’ve been surveying them for a number of years for different viruses, and we found several viruses that they carried and [that] were associated with mild disease. Subsequent to that, we had this disease in the polar bear which developed a fatal, or severe, encephalitis, and we were able to go back to all our database of different viral agents we’d found, and we could see that the polar bear virus was the same as a virus that had been detected in zebras years before.

That’s the current belief, that it is indigenous to zebras. They can experience mild disease, but they do not typically experience severe disease, which is very characteristic of herpes viruses in general.

There were some zebras temporarily located near the polar bears, but there was a significant barrier between them — a 200-foot dry-land barrier. It’s really not clear how that virus was transmitted to the polar bear. But the investigation suggests that — or what’s really significant about the investigation is that the virus appears to be highly infective, because there are all kinds of precautions taken to protect animals that are in adjacent, or different, parts of the zoo.

So we really don’t know exactly how it got there. It could have been from a mechanical vector, such as an insect. It could have been some type of windborne fomite that transmitted it to the polar bear. In both of those cases, the really compelling nature of the finding was that the virus would be highly infectious and pathogenic, and that’s what has been found in other zoological institutes as well.

This is the first case of a polar bear, or any type of bear, contracting this virus, and it is the second part of this investigation that is highly significant in that this virus, by affecting the polar bear, demonstrated that it’s capable of crossing wide taxonomic animal groups, which is not usually typical of herpes viruses. So it’s a particularly important finding to be aware of.

Herpes viruses have been studied for many years. They’re problematic in people but don’t typically cause [severe problems] except in immunocompromised or immunosuppressed individuals. However, there are certain zoonotic herpes viruses that come from primates that are of great concern to human welfare, and those have been studied in great depth. Those viruses, however, do not jump across the wide taxonomic groups like this one did. So this is a very important virus to study, because it could lead to important information about how viruses become zoonotic, or transmissible between animals and humans.

There are other researchers in Japan and in the United States who are very interested in this virus, and they’re studying its genetic composition and looking at potential ways that it can have such a promiscuous nature or ability to infect so many different types of animals. We here are not actively doing any more research other than to continue our surveillance and to provide samples of the virus to other investigators.

It’s largely gone unnoticed, because this virus is very similar, or related to, a previously described virus in horses. The equine herpes virus 1 is a virus of domestic horses and is present in many horse populations throughout the world. This virus [the one we had here] kind of went under the radar for a number of years, because it’s very similar to that virus.

It was presumed to be just a sub-strain of it, but now we know through more advanced genetic analysis that it is a separate species of virus. It may have — this is just speculation — but it may have arisen from the equine virus many years ago.

There are certain viruses that can infect almost any type of mammal — for example, the rabies virus. For a herpes virus, this is a unique type of virus, because it’s now infected animals in three different orders, which is very unusual.

It’s infected artiodactyls, which include host stock in ruminates — for example, giraffes and gazelles. It’s infected equids like the zebras, as well as onager, and now it’s infected an ursid, which is the polar bear. Those are three widely different taxonomic groups of animals. In all cases, infection has been naturally occurring. That led to a lot of people being interested in this virus as a potential threat to many animals as well as people. So as some researchers have done — in Japan — [they] have done inoculation studies and found that the virus can also infect rodents, cats, dogs, goats, sheep, and primates.

[Infection in humans] has never been documented, but that is a potential worry. And that is a very primary focus now of the National Institutes of Health, developing programs and funding for looking at viruses that have the potential to become zoonotic or to infect people. And much of that research has been driven by the recent outbreaks of SARS and avian influenza, the highly pathogenic influenza, both of which have been extremely costly and detrimental to human health. Now the NIH is really focused on How can we find viruses that are on the verge, or have the potential, of becoming zoonotic? And this is one of the types of viruses that they would be very interested in. — Matt Potter

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