The Raccoon Polyomavirus Genome and Tumor Antigen Transcription are Stable and Abundant in Neuroglial Tumors
Drs. Pesavento and Woolard and their students recently published an important paper in the Journal of Virology showing that raccoon Polyomavirus is present in neurological tumors. The study highlights several ways in which SVM faculty are collaborating on research that makes timely discoveries about important health issues involving viral transmission of disease. The study also underscores the key role contributed by graduate students and undergraduate students in the research performed in the SVM.
Key Findings: The natural lifecycle of the Polyomaviruses (PyVs) that infect humans and other animals is to persist without causing disease, however certain PyVs can cause cancer in humans or in other animals. The oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models because naturally occurring viral associated tumors are unpredictable. The Pesavento laboratory discovered raccoon polyomavirus (RacPyV), which is 100% associated with neuroglial tumors of free-ranging raccoons in the Western United States. While this virus-brain tumor association is, to date, intractably linked, a robust collection of scientific evidence is needed to support the classification of RacPyV as a causative agent in raccoon neuroglial tumors. In this paper, the researchers demonstrate that the RacPyV genome and transcription of the virally encoded oncogenic T-antigen are abundant in primary tumors, metastasis, xenotransplants, and cultured primary tumor cells. Throughout all of these manipulations, RacPyV was found to be stable as an episome (non-integrated) which demonstrates a minimal criterion for causation and a novel mechanism of polyomavirus associated oncogenesis.
Bartonella are blood-borne bacteria infecting a wide variety of domestic and wild animal species. One species, Bartonella vinsonii subsp. berkhoffii (B. v. berkhoffii), is known to cause severe cardiac disease by destroying the cardiac valves (endocarditis) in domestic dogs and humans. Coyotes are the main reservoir for B. v. berkhoffii, but it was not known if infected coyotes developed endocarditis like their domestic counterparts.
Therefore, Spencer Kehoe (DVM Class 2015) and his STAR mentor Dr. Bruno Chomel (Department of Population Health and Reproduction) hypothesized that coyotes serve as a naturally-occurring epidemiological and physiological sentinel models to study infection kinetics and pathology caused by this bacterium in reservoir (coyotes) and accidental hosts (humans/ dogs).
While hepatotoxicity following acute exposure to toxins produced by algal called microcystins is well documented, neurotoxicity after sub-lethal exposure is poorly understood. Caroline (Carly) Moore, a VSTP PhD/DVM student working with Dr. Birgit Puschner, has developed a novel statistical approach to analyze neurotoxic effects in a convenient model organism, the adult nematode (Caenorhabditis elegans). Alga known as Cyanobacteria are some of the oldest and simplest organisms still inhabiting fresh, brackish and marine waters. While some algal blooms are harmless, others have the potential to produce various toxins, with the first documented case of cyanobacteria poisoning described in 1878. Algal toxins known to be very resistant to degradation are called microcystins. At high doses, microcystins are acutely hepatotoxic. Microcystins have resulted in illness in humans and death in wildlife, livestock, dogs and humans for many years. Surprisingly, there are no federal regulations to test for microcystins in recreational or drinking water, fish and seafood, or blue-green algal supplements such as spirulina (a component of many commercially available superfood green drinks). In fact, when samples of blue-green algal supplement tablets were tested for microcystins, 85 out of 87 samples (98%) had detectable levels of microcystins. This raises concerns whether non-lethal exposure to microcystins can cause toxicity. Recent studies have linked chronic exposure to microcystins to liver and colorectal cancer in humans. Microcystins may also cause neurotoxicity as patients exposed to microcystin-contaminated water during dialysis treatment experienced neurological symptoms. The research featured here set out to establish the alternative model Caenorhabditis elegans (C. elegans) as a robust platform to study microcystin’s potential to cause neurotoxicity. C. elegans are remarkable 1 mm clear worms, which have predictable behaviors associated with specific neurons. Due to their ease of care (they eat non-pathogenic E. coli and can be stored on the bench or at -80 degrees), thoroughly understood genetics (the whole genome and 302 neurons are mapped), and short lifespan (about two weeks), the C. elegans model has many advantages over traditional in vivo models. With many conserved biological functions between humans and C. elegans, we were able to use the established C. elegans neurotoxicity model in the investigation of the potential of non-lethal levels of microcystins to cause neurotoxicity.
American Society of Microbiology (ASM) Responds to CDC Anthrax Exposure
The recent events at the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH), which are documented in the report below, reveal significant lapses in biosafety, biosecurity, oversight and compliance with the Select Agents and Toxins regulations. At every level, in teaching, research, and diagnostic laboratories, microbiologists must take all steps possible to guarantee biosafety, to protect themselves, their co-workers, and the broader public from microorganisms that can cause disease. Microbiologists who work with dangerous pathogens have a responsibility to understand and comply with biosafety and biosecurity regulations. As such, ASM members must ensure that they are acting with the highest level of responsibility and accountability in their laboratories.
Microbiologists engage in activities that are essential to detect, respond to and prevent infectious diseases. This work must be conducted as safely as possible. Toward that end, we urge microbiologists to review their laboratory procedures and to ensure that they are compliant with biosafety regulations and best practices. Microbiologists and institutions should regularly inventory all areas of storage to maintain an accurate and up-to-date inventory of materials to be certain there are no unaccounted for infectious agents and toxins. Identified lapses in biosafety and biosecurity must be reported promptly to the appropriate institutional authorities. Public health and safety are of the utmost importance and we have a professional responsibility to maintain the public trust.
The following is a link to the CDC’s July 11 Report on the Potential Exposure to Anthrax http://www.cdc.gov/od/science/integrity/docs/Final_Anthrax_Report.pdf.
UC Davis veterinarians mentioned in Futurist article on Expanding Pet Longevity
Bruce Alberts, Marc Kirschner, Shirley Tilghman, and Harold Varmus describe specific ways for "rescuing U.S. biomedical research from its systematic flaws" in this week's Proceedings of the National Academy of Science. They write, "The long-held but erroneous assumption of never-ending rapid growth in biomedical science has created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession-and making it difficult for seasoned investigators to produce their best work. This is a recipe for long-term decline, and the problems cannot be solved with simplistic approaches." The authors suggest reforms on the funding of graduate students, postdoc compensation, and peer review. They also would reconsider rules on indirect facilities cost reimbursement and salary support on research project grants.