Geoffrey Holm, Colgate University

Ella Monfort, Ana Jimenez, Geoffrey Holm, Department of Biology, Colgate University

Cell Biology of Viral Infection

Approximately 1.6 million humans and 4.2 million dogs are diagnosed with cancer yearly in the USA. As with humans, dogs are susceptible to different types of tumors, and due to the selective breeding of domestic dogs, they exhibit high incidences of inherited disorders, including cancer. Large-breed dogs typically have shorter lifespans and an increased propensity for cancer. Additionally, older dogs, especially those of larger breeds, have significantly higher glycolytic phenotypes than long-lived smaller breeds. This suggests that cells from larger breeds may be metabolically predisposed to a tumor-like phenotype. Mammalian reoviruses infect the intestinal tracts of most mammals, including dogs, and can infect most cell types, including fibroblasts, though they replicate to higher levels, and cause more cell death, in transformed cells. As a result, reovirus is being developed as an oncolytic virotherapy (OV), in both humans and canines. However, relationships between reovirus susceptibility, cellular metabolism, and oncolysis are not fully understood. We used primary dog fibroblasts derived from different breeds, ages, and sizes to test these relationships. Cells derived from older dogs were found to be significantly more susceptible to reovirus infection than cell lines from younger dogs. Additionally, reovirus T1L caused significant increases in both the basal Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) in cell lines from older dogs, suggesting that infection results in cell line-specific metabolic alterations. Continuing experiments aim to further delineate the relationships between metabolism, reovirus susceptibility, and age, with the aim of increasing the effectiveness of OV for humans and canines.