Monday, 25 November 2019 | 3:00 pm
Professor and Interim Chair, Department of Developmental, Molecular and Chemical Biology Tufts University School of Medicine, Boston, MA, USA
Oncogenic Activities of Human Papillomaviruses
(Host: L. Banks)
At least 5% of all human cancers are caused by infections with human papillomaviruses (HPVs). The high-risk mucosal HPVs cause almost all cervical carcinomas, a significant number of other anogenital tract cancer and a growing fraction of oral cancers. These cancers are driven by expression of the viral E6 and E7 proteins and expression of these two proteins is necessary for induction as well as the maintenance of the cancerous phenotype. E6 and E7 have no intrinsic enzymatic activities and do not directly interact with specific DNA sequences but they function by associating with hist cellular regulatory proteins and protein complexes. Some cutaneous HPVs also contribute to carcinogenesis and have been linked to keratinocyte carcinomas, particularly squamous cell carcinomas in long-term immunosuppressed organ transplant patients and in individuals afflicted by a rare genetic disease, epidermodysplasia verruciformis. Here, the viruses contribute to cancer initiation but are not necessary for tumor maintenance. Interestingly, the E6 and E7 proteins have evolved to target different cellular pathways than E6 and E7 encoded by high-risk mucosal HPVs. A recently identified papillomavirus that infect laboratory mice shares some cellular targets with cutaneous HPVs and is a useful model to study the oncogenic activities of these viruses in vivo.