Strategic Communications and Marketing News Bureau

Connecting a virus to cancer – in sea lions

Colegrove at work in the Zoological Pathology Program Laboratory.

Colegrove at work in the Zoological Pathology Program Laboratory.

CHAMPAIGN, Ill. – I distinctly remember the first day I saw the images proving our hypothesis about the connection between a herpesvirus and urogenital cancer in wild California sea lions. Our research team was the first to use a revolutionary technique to probe preserved cancerous tissue from marine mammals as we looked for signals of specific viral genes.

And we found them: Wherever there was tumor, there also was a strong signal of multiple cancer-promoting viral genes, called oncogenes. There were no viral genes in the adjacent cancer-free tissue. This meant that the virus clearly played a role in cancer development and was not merely a bystander in the animals’ reproductive tracts.

To say the images made us pathologists excited is an understatement. It was a eureka moment that was a long time in the making.

I began investigating cancer in sea lions 18 years ago when I was a Ph.D. student at the University of California, Davis working with The Marine Mammal Center in Sausalito, California. My role as lead pathologist for the sea lion cancer project continued after I joined the Zoological Pathology Program at the U. of I. College of Veterinary Medicine.

Aerial photo of thousands of sea lions gathered on the breeding beaches of San Miguel Island.

Thousands of sea lions gather on the breeding beaches of San Miguel Island, one of the Channel Islands off the coast of Southern California.

Over the years, I’ve examined the reproductive tissues of hundreds of sea lions, so many that I’ve come to think of myself as a bit of a sea lion gynecologist.

I’m by no means working alone. This research is part of a multi-institutional initiative. The Sea Lion Cancer Consortium brings together a team of clinicians, pathologists, marine mammal biologists, virologists, toxicologists and epidemiologists from institutions around the world.

Our data set on free-living California sea lions is one of a kind. Because these animals develop cancer under real-life conditions – as opposed to having their cancers artificially induced in a laboratory – our findings are more likely to be relevant to other free-living populations, including people.

Labeled cancer tissue from a California sea lion showing positive pink signaling for the otarine herpesvirus-1 BCL-2 oncogene within the tumor.

Labeled cancer tissue from a California sea lion showing positive pink signaling for the otarine herpesvirus-1 BCL-2 oncogene within the tumor.

One in four adult sea lions examined at The Marine Mammal Center has cancer. A robust case-control study requires a large population that includes individuals with and without cancer. Over the past 20-plus years, we have amassed enough pathologic, toxicologic and viral data to make firm conclusions about the causative factors of cancer development in sea lions.

In a new article in the journal Animals, led by Dr. Alissa Deming of the University of Florida, Gainesville, we report on tissues from 95 sea lions with an aggressive and deadly form of cancer, and 163 without. We found herpesvirus in 100% of the sea lions with cancer, along with exceptionally high viral loads and viral gene expression within the genital tumors. Although 36% of the sea lions that did not have cancer tested positive for herpesvirus, these animals had much lower viral load and no detectable viral gene expression, indicating that the herpesvirus was dormant.

Of course, our findings will benefit sea lions. Veterinarians at the Marine Mammal Center and other wildlife institutions will be better able to assess the prognosis for stranded animals simply by evaluating their viral load. Otarine herpesvirus 1, the virus that is our focus, likely can lie dormant in sea lions and not cause cancer; these animals will have a low viral load. Sea lions with a high viral load are more likely to have aggressive cancer even if they exhibit no outward signs.

Our research could benefit human cancer patients as well.

California sea lions are top-level predators living in coastal areas with a large historic burden of the pesticide DDT, as well as other organochlorines. These “legacy” contaminants are slow to break down; they persist in California coastal waters even though DDT production was banned in 1972.

Who, besides sea lions, swims in and eats seafood from these waters? We do. Humans are likely exposed to the same environmental pollutants as sea lions. And we already know that viral infections play a role in up to 20% of human cancers.

We hypothesize that, similar to other virally induced cancers, the cancer in sea lions involves additional triggers that activate the virus, spurring malignancy in individuals. By examining the interplay between viral infection, chemical exposure and cancer development, studies like ours may help explain how everyday environmental exposures in the water or air can impact human health and affect tumor growth.

Editor’s notes:

Dr. Kathleen Colegrove is a co-author of the study “Unlocking the role of a genital herpesvirus, otarine herpesvirus 1, in California sea lion cervical cancer.” She is part of the College of Veterinary Medicine’s Zoological Pathology Program, which partners with terrestrial and aquatic wildlife conservation organizations from every continent except Antarctica. Colegrove is a founding member of the Sea Lion Cancer Consortium. For a news release about the study, see also: Herpesvirus triggers cervical cancer affecting nearly 1 in 4 adult sea lions

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