Tumor Viruses: Oncogenic Microbes and Tools for Discovery
The first scientific report of a tumor caused by a virus was published in the early 1900s. For more than a century following this discovery, scientists have continued to identify and study these viruses that cause tumors in their hosts, which are now known as tumor viruses. There are currently 7 known tumor viruses that cause cancer in humans, and together these viruses are responsible for more than 15% of the global cancer burden. Decades of basic scientific research on tumor viruses have not only contributed to our understanding of how viruses can cause cancer, but also fortuitously yielded fundamental discoveries in cell and molecular biology. Important biological principles such as RNA splicing, reverse transcription, DNA repair mechanisms, host tumor suppressors, oncogene addiction, restriction enzyme mapping/cloning, and the establishment of several of the most commonly used cell lines in biomedical research were all discovered through the study of tumor viruses.
Merkel Cell Polyomavirus
Merkel cell polyomavirus (MCPyV) was discovered in 2008 and is the first human polyomavirus etiologically linked to a human malignancy, Merkel cell carcinoma (MCC). MCPyV infection is ubiquitous in the human population, yet relatively little is known about its cell tropism, natural life cycle, and transmission. It is hypothesized that the virus has tropism for one or more cells within skin, yet Merkel cells themselves are unlikely target cells for infection. Notably, normal Merkel cells arise from epithelial progenitor cells within the skin although dermal fibroblasts are, so far, the only cell type found to support the complete MCPyV life cycle. For these reasons, epithelial keratinocytes and dermal fibroblasts are currently the two most plausible skin cell types hypothesized to be the natural host cell for MCPyV infection and/or cell of origin for MCC. Emerging evidence suggests that MCPyV early viral proteins may be involved in driving infected cells towards a Merkel cell lineage under certain conditions, but our understanding of this process remains limited.
The Spurgeon Laboratory studies the mechanisms by which MCPyV early viral proteins cause MCC in human skin cells using both two- and three-dimensional in vitro tissue culture models. We also use a transgenic murine model of MCPyV T antigen expression to further explore virus-induced MCC development.
Human Papillomaviruses
Human papillomaviruses (HPVs) are a large family of DNA viruses that infect tissues found at various anatomical sites, including the skin, anogenital tract (cervix, vagina, anus, penis), and oral cavity. HPVs are the most common sexually transmitted infection and the oncogenic high-risk HPV types together cause at least 5% of human cancers worldwide. The Spurgeon Laboratory specializes in the development and use of preclinical infection models to study host-pathogen interactions that underlie the transmission, pathogenesis, and oncogenic potential of HPVs. Using a murine papillomavirus (MmuPV1), we have developed infection models of cervicovaginal carcinogenesis and papillomavirus sexual transmission.
Using these models, the Spurgeon Lab is focused on two main areas of HPV research: 1) the dynamics of papillomavirus sexual transmission and sex-specific differences in pathogenesis and 2) exploring the bidirectional interplay between the host cervicovaginal microbiome and papillomavirus infection. These genetically tractable models provide powerful platforms in which to investigate host-pathogen interactions that underlie persistent papillomavirus infections and neoplastic disease, as well as potential therapeutic approaches to treat papillomavirus-induced cancers.
