All living things are infected with viruses.

As humans, we have viruses living in us and on us, some of which we get infected with as children and keep for life. These “persistent” infections, for the majority of us, will never pose any health concerns. If they do, it’s due to major problems with our immune systems.

On the other hand, viruses can also come and go repeatedly throughout our lives causing various degrees of illness. Consider those that cause the cold and flu. These are more “acute,” short-term infections that show up, run their course, and then go away with the help of our trusty immune systems. There are exceptions (the very young, very old, or those with compromised immune systems—who may experience these infections more severely), but in general, most of us tough it out and move on.

These two scenarios have been studied by virologists and biomedical scientists for decades. With the advent of metagenomics, our understanding of viral diseases has been challenged.

Metagenomics is essentially the study of all the genetic material in a sample, in order to establish what’s “living” in that sample. The technology gets better, faster, and cheaper on an almost daily basis, leading to:

1. The detection and discovery of viruses anywhere we look from dirt and seawater, to sewage, even to store-bought poultry, beef, and fish…
2. The realization that many infectious diseases are “polymicrobial.’ In other words, it is likely that more than one bug contributes to symptoms at any given time.
3. The discovery of the same virus in both diseased and completely healthy individuals (animal or human).

In the Disease Investigations group, we are using metagenomic analyses for both discovery of new potential pathogens, and monitoring populations of ones we already know about. As veterinary pathologists, we do post-mortem examinations and microscopic evaluation of tissues to figure out cause of death. We often see microscopic changes that make us suspicious of a viral disease. If we test for viruses we know about and come up empty handed, this is where the power of metagenomics comes in.

What does this have to do with red pandas?

During my PhD at UC Davis, my advisor utilized metagenomics on a regular basis, including the discovery of the canine virus on which my PhD was based. In 2014, she evaluated a very old red panda from the Sacramento Zoo that died with microscopic changes suspect for a viral disease. Tissues were submitted for metagenomics analysis, and a new virus called an “amdovirus” was identified. This virus is in the same family as much more widely known canine parvovirus and feline panleukopenia virus (if you have a dog or cat, they are very likely vaccinated for these).

After initial discovery, pathologists have a unique and important role in determining whether newly discovered viruses pose a health threat to the population. Remember that  many viruses can be present without really doing anything. Could this new red panda virus just be a red herring?

To answer this, we decided to screen archived red panda tissues from both the Sacramento and San Diego Zoo. Additionally, we screened feces from all of the living red pandas currently housed at both institutions. We found virus in archived tissues from diseased pandas, normal tissues, AND feces from live animals at the Sacramento Zoo, who are completely happy and healthy. So far, feces from San Diego Zoo red pandas have tested negative. The work from the Sacramento Zoo was in large part conducted by our soon-to-be Steel Endowed Pathology Resident, Dr. Charlie Alex! The lab work involving testing of SDZ red pandas is being conducted by Maya Schlesinger, an undergraduate, pre-veterinary student from the University of Connecticut. She is one of our Summer Fellows working under the generosity of the J.W. Sefton Foundation.

What does this have to do with conservation of endangered species?

It is extremely complex to try to figure out all the reasons as to why a virus can kill one animal and have no effect on another. Many viruses evolve very quickly. When they do, new strains emerge that may cause more severe disease than usual. Did the red pandas that got sick just happen to be infected with a worse strain of the virus?

Additionally, viruses can evolve the ability to infect new host species. We know that skunks, raccoon dogs, and gray foxes all carry around amdoviruses. Could a wild animal have transmitted this virus to red pandas at some point? Or, could this be one of those “persistent” infections of red pandas that becomes a problem only when they get really old and have problems with their immune system?

These scenarios are relevant to conservation. Wildlife habitats all over the world are shrinking due to human population expansion and development. As such, animals are coming into contact domestic animals like livestock and companion animals as well as other wildlife species they’re now forced to share their home range with. This creates the perfect opportunity for infectious disease transmission. Additionally, habitat loss and increased animal density creates stress – a major factor in susceptibility to infectious diseases. Suddenly, that persistent infection takes advantage of a stressed out immune system and rears its ugly head…

My hypothesis so far is more aligned with that last scenario - that red panda amdovirus can cause disease sporadically in individual animals when they are in a more susceptible state but does not currently pose a significant health threat to the population at large.

Overarching goals of this project are several-fold. One is to educate our zoo veterinarians and keepers about potential infectious disease risks at the Zoo. It also established new research tools as valuable additions to our Molecular Diagnostic Lab. Finally, the steps we took to address the presence and significance of this virus will serve as a model for Disease Investigations group to fulfill our mission statement: Removing disease as a roadblock to conservation.