Viruses need to traffic from the cell surface to their sites of replication to cause infection. For many viruses with DNA genomes, that location is the nucleus. Despite their impact on public health, mechanisms of virus infection are often poorly understood. Clarifying how viruses gain entry into cells has the potential to identify new therapeutic targets against these human pathogens as well as to contribute to our understanding of various aspects of cell biology in general.

Cancer remains one of the leading causes of death worldwide, with tumor viruses being responsible for up to 15% of those cases. The study of such viruses is essential for public health and will help to limit viral transformation while providing invaluable insight into the mechanisms of cancer progression.

Research on one of the best characterized DNA tumor viruses, polyomavirus (PyV), has led to major scientific breakthroughs in both the cancer and cell biology fields. Over the past several years, eleven new PyVs have been identified, including Merkel cell PyV (MCPyV) — the etiologic agent of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Despite the nomenclature, McPyV does not initially infect Merkel cells and the cellular tropism and transmission route remains unclear. Our lab seeks to decipher the viral entry requirements of McPyV, which will lead to better infection models for understanding tumor virus induced disease.

Oncolytic viruses (OVs) are viruses that specifically target and kill cancer cells while leaving healthy cells intact. This virotherapy approach exploits the susceptibility of cancer cells to virus infection, but it requires high specificity and potency of infection to be successful. Despite significant advances, OV therapy has been limited, in part due to the inefficiency of these viruses in establishing infection.

Several DNA viruses have been considered as candidates for OV therapy, including the non-enveloped parvovirus (PV), which is currently in clinical trial for glioblastoma. Similar to other DNA viruses, PV must deliver its genome to the nucleus, but its mechanism of nuclear entry is unclear. Because nuclear entry often represents the major bottleneck in virus infection, our studies will increase the foundational understanding of OV entry to enable optimal therapeutic design.