Several important virus families can only establish an infection, if they invade dividing cells. They require cell division in order to deliver their genome in a replication competent form into the nuclei of cells, as during cell division the nuclear envelope, a protective border to the cytosol, is removed during cell division giving these viruses access to the nuclear lumen. In this project, we have followed up two main questions: On the one hand how do small DNA tumor viruses of the papillomavirus family, i.e. viruses that lead to malignant cancers, mechanistically use host cell division to enter host cells, a mechanism of viral invasion that is barely understood. On the other hand, we used such papilloma viruses as a model virus to address how intrinsic and extrinsic changes to cellular context (such as (chronic) inflammation, wounding, prior infection, and ageing) affect this process and thus the outcome of infection. The latter has been documented but why these processes affect virus infection is not understood.
Since infections of human papillomaviruses pose a severe health risk through the development of anogenital and oropharyngeal cancers, our work may allow the development of better preventative and possibly personalised treatment options.
The overall objectives aim at understanding of these human papillomaviruses infect cells under a variety of conditions, but also to experimentally establish systems that allow to study how viruses in general are impacted by physiological and pathophysiological changes that arise during our life time. The latter implies that besides our genetic background, the way our lives have been influences our susceptibility to viral infections, a feature that has been observed in epidemiological studies, but that remains mostly inaccessible to experimentation. But as long as we cannot understand the underlying cause for different susceptibility, we may not be able to protect ourselves from infections depending on our personal history.
