Now a team of researchers from the University of Pennsylvania School of Veterinary Medicine and Penn's Perelman School of Medicine has the first evidence that an Epstein Barr-like virus can infect and may also be responsible for causing lymphomas in man's best friend.
The findings suggest that domestic dogs possess a similar biology to humans with respect to EBV infection. That could allow scientists to study dogs to help uncover the mechanisms by which EBV leads to cancer in certain people.
"There are no large-animal spontaneous models of EBV infection and virus-associated disease, and most studies investigating viral disease are performed in non-human primates, which are very expensive," said Nicola Mason, senior author of the study and an assistant professor of medicine and pathobiology at Penn Vet. "Discovering that dogs can get infected with this virus like people do may provide us with a long-sought-after model for EBV-associated disease."
Mason's team at Penn Vet included Shih-Hung Huang, Philip Kozak, Jessica Kim, George Habineza-Ndikuyeze, Charles Meade, Anita Gaurnier-Hausser and Reema Patel. The team worked closely with Erle Robertson, professor of microbiology at the Perelman School of Medicine.
Their work was published online March 8 in the journal Virology.
In humans, the Epstein Barr virus infects B cells. After an acute phase of infection, of which many people are not even aware, the virus goes into a latent phase. Most people show no symptoms during this phase, but, in some, EBV promotes unnatural growth of B cells, which contributes to the development of lymphoma.
Meanwhile, dogs develop lymphomas that share some characteristics with the human equivalents. These conditions are relatively common in certain breeds. In golden retrievers, for instance, one out of every eight dogs develops lymphoma.
Yet, "the paradigm up until now was that EBV only infects humans," Mason said. "It is an extremely successful virus, and most people are infected. Since humans and domestic dogs have cohabited for around 15,000 years, we hypothesized that the virus may have adapted to another host. "
To search for evidence of infection, Mason and colleagues obtained samples of blood from client-owned dogs of various breeds brought to Penn Vet for care. In 48 dogs with lymphoma and 41 without the disease, the researchers first looked to see if the pets had antibodies against proteins specific to the EBV capsid, the protein shell of the virus. The test is nearly identical to one that physicians use to detect exposure to EBV in humans.
The researchers observed that eight of the dogs with lymphoma and three of those without it had high levels of antibodies against EBV proteins, indicating that a portion of the dogs had been exposed to a virus very similar to EBV.
While the presence of antibodies confirms that a dog has been exposed to a virus, the team wanted to know whether the virus had a direct association with the tumors in dogs with lymphoma. Finding viral elements, including DNA, within lymphomas in humans is an indication that the tumor is associated with the virus, therefore Penn researchers looked to see if they could find virus in the dog tumors.
Using the polymerase chain reaction, which amplifies specific DNA sequences, the researchers analyzed lymph nodes of dogs with and without B cell lymphoma. In two dogs with lymphoma, they were able to identify a portion of DNA very similar to a sequence in EBV. They found no evidence of the same DNA in the healthy dogs.
They repeated similar tests with other stretches of EBV DNA, finding evidence of EBV-like DNA in the cancer cells of three of nine dogs with lymphoma. They also identified a virus-associated protein in the malignant lymph nodes of two of nine dogs with lymphoma.
Finally, examining cancerous B cells under an electron microscope revealed what appeared to be viral particles, similar to what what has been seen in the tumor cells of humans with EBV-linked lymphomas.
Taken together, the researchers' discoveries indicate that some dogs are naturally infected with a virus similar or identical to EBV and that, as in humans, the virus appears linked in certain cases with canine lymphomas.
That such a large percentage of humans are exposed to EBV and yet only a small fraction develop cancers indicates that there may be a genetic component to EBV-associated cancer susceptibility.
"With additional studies within certain breeds of dog," Mason said, "we hope to provide insights into genetic factors that may predispose to virus associated lymphoma. Furthermore, this spontaneous dog model may help us evaluate new treatments for EBV-related lymphomas or investigate strategies to prevent those cancers from developing in the first place."
The study was supported by the University of Pennsylvania's Veterinary Center for Infectious Disease, the Abramson Family Cancer Research Institute at the University of Pennsylvania and the National Cancer Institute.
Katherine Unger Baillie | EurekAlert!
Further reports about: > B cells > Burkitt's lymphomas > DNA > DNA sequence > EBV > EBV proteins > EBV-associated disease > Epstein Barr-like virus > Medicine > Veterinary Public Health > development of lymphoma > domestic dogs > kissing disease > lymph node > lymphoma > mononucleosis > non-Hodgkin's
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction