The Van Doorslaer lab at the University of Arizona

Using -omics to study the evolution of papillomavirus disease

As demonstrated by the COVID-19 pandemic, viruses have the potential to drastically disrupt daily activities and result in substantial loss of life. Viruses are selfish replicators. They infect a host and use the cellular machinery to replicate (i.e., make new infectious copies of themselves). Our research investigates how a virus tricks the cell’s machinery into making more copies of the virus. Specifically, our research focuses on cancer-causing human papillomaviruses. Infections with human papillomaviruses (HPVs) are the most common sexually transmitted infection in the US. HPVs are responsible for an estimated 5% of cancers worldwide. Following infection, the virus needs to change the cellular environment to persist (i.e., infect the host for a long time, months to years) inside the infected cell. Importantly, to cause cancer, a virus must persist inside the host. Acute HPV infections, per se, do not cause cancer . Thus, understanding the evolutionarily conserved mechanisms of virus-host interplay that promote or restrict viral persistence has important implications for HPV biology and human cancers. Understanding how a virus co-opts the cell will allow for the design of targeted therapeutics, which are sorely missing for HPV-positive cancers.

We want to know how these viruses establish long-term infections. We approach this question from different angles using complementary experimental approaches. The study of viral evolution is a guiding principle in all this work. Importantly, when the virus causes cancer, the cellular machinery that copies the virus is no longer functional. This means that when a virus causes cancer, it essentially commits suicide in the process. The theory of evolution would suggest that cancer-causing would not be selected, yet these viruses are potent cancer-causing agents. We became interested in this conundrum. We believe that while causing cancer is not a goal, the ability to infect a person for a long time (and thus increase the time available to the virus to reproduce) is a substantial evolutionary benefit for a virus. We hypothesize that causing cancer is a side-effect of the virus trying to make a long-term home inside the cells of a patient. Therefore, if we understand how the virus achieves this goal, we will be able to design specific therapeutic interventions to prevent or cure cancers caused by human papillomaviruses. We are one of only a few labs tracking the viral lifecycle from infection to cellular transformation.

We have several projects in the lab using a combination of state-of-the-art tissue models, genomics, and evolutionary analyses to study the interplay between the virus and the host throughout infection .