Tuesday 5 July 2022 | 12:00 noon – Cape Town, SOUTH AFRICA

Laboratory for Environmental and Life Sciences, University of Nova Gorica, SLOVENIA

Human papillomaviruses interfere with host cell processes during infection

(Host G. Schäfer)

Human papillomaviruses (HPV) are non-enveloped DNA viruses that infect skin and mucosal epithelial cells and cause hyperproliferative lesions. Of the nearly 200 different genotypes, about 24 high-risk HPV genotypes are causally associated with various cancers in humans, including nearly all cervical cancers, other anogenital cancers, and an ever-increasing number of head and neck cancers. Despite effective vaccination against a number of the most carcinogenic HPV types, HPV-related disease remains a major health concern worldwide. ItisgenerallyacceptedthatHPVviruseshijackproteinsinvolvedinintracellulartraffickingandother cellular processes to facilitate infection. However, virus-host protein interactions can also disrupt these processes and thus have broader implications for cell physiology and pathophysiology. The first part of the talk will focus on the interaction of the HPV minor capsid protein L2 with the host trafficking machinery, specifically Sorting Nexin 17 (SNX17). While interaction with host cell sorting machinery supports viral infection, there is also the possibility that normal cellular recycling pathways are disrupted by HPV infection. In the second part, some recent data on the role of APOBEC3 (A3) proteins in HPV oncogenesis will be presented. A3 proteins, which are part of the innate immune response, act as a restriction factor against HPV infection by reducing the level of primary infection and the infectivity of HPV virions. However, this intrinsic host defence mechanism is also responsible for long-term host DNA hypermutation and cancer development in persistent HPV infections.