Periodic Reporting for period 3 - MitoVin (Mechanism and Consequences of the Interplay between Mitosis and Human Papillomavirus Initial Infection)
Reporting period: 2019-10-01 to 2021-03-31
In this project, we address on the one hand how small DNA tumor viruses of the papillomavirus family mechanistically use host cell division to enter host cells. On the other hand, we aim to understand how intrinsic and extrinsic changes to cellular context (inflammation, wounding, prior infection, and ageing) affect this process.
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.
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.
Investigations into how papillomaviruses exploit host cell division to gain access to the nuclear space for infection have identified several cellular targets that are hijacked for this purpose. Moreover, we have identified on the viral side a peptide in a crucial viral protein that mediates these interactions, Besides a more thorough understanding of viral infection, we think it an option to exploit this information for the development for second or third generation vaccines for this health risk. Moreover, all experimental systems have been established that mimic dedicated intrinsic and extrinsic changes to cellular context, i.e. physiological and pathophysiological changes that arise during our life time. With this, we could confirm some of the epidemiological data, so that we can now investigate the underlying reason for their impact in infectivity.
We expect that at the end of the project, we will have tested whether the development of next generation vaccines would profit from our results. Moreover, we are confident that we will have a detailed understanding on how papillomaviruses exploit cell division for infection. Lastly, we hope to make great strides towards an understanding as to why physiological and pathophysiological changes to cell state influence susceptibility to infection.