UMaine viral study earns $440K from the National Institutes of Health

A University of Maine study of the behavior of a virus that can lead to deadly brain disease was recently awarded $440,410 from the National Institutes of Health. 

The study looks at how the virus, known as JC polyomavirus (JCPyV), interacts with receptors on human host cells. Little is known about how the virus infects human cells, even though JCPyV affects up to 80% of the population and causes chronic kidney infection in hosts. In immunocompromised patients, however, JCPyV can also cause progressive multifocal leukoencephalopathy (PML), a deadly brain disease that destroys the protective layer around its nerve fibers. If left unattended, it can be fatal within a year.

The project is led by Melissa Maginnis, associate professor in molecular and biomedical sciences, in collaboration with Samuel Hess, professor of physics. Based on the findings of previous studies, the researchers hypothesize that a certain type of serotonin receptors, a subfamily known as 5-HT2Rs, let JCPyV enter the cells. Once inside, the virus recruits more of those same receptors into clusters to ferry more JCPyV into the cell. 

With the NIH funding, Maginnis and her team will look at the mechanisms that cause these clusters of serotonin receptors to form, how these clusters trigger the signals that cause more viral infection, and whether these receptors and their associated proteins bring the virus to the endoplasmic reticulum, the part of the cell that creates proteins and delivers them throughout the body.

“This grant allows us to continue exciting work in (our) lab to uncover how viruses modulate cellular receptor functions to facilitate viral invasion of host cells. Moving forward, we will define how cellular signals initiated from the receptor prime the cell for viral infection, ultimately preparing the cell for a virus takeover,” Maginnis says.

Understanding this process of viral entry could be the key to developing treatments that can address PML. The findings could also provide more insight into how other similarly structured viruses — including coronaviruses, herpesviruses and hemorrhagic fever Ebola and Marburg viruses — enter cells and activate the cellular signals that allow them to spread.

The lab work for the study is innovative and well-suited for student training. Preliminary data for the studies was gathered entirely by UMaine graduate and undergraduate students. UMaine graduate students in Maginnis’ laboratory will work on the next steps of the project for their dissertation research projects. Portions of the projects will also be used as independent projects for undergraduate researchers. 

“This project provides excellent student training opportunities through which they develop and hone their laboratory skill set, using viruses as tools to ask probing questions about cell biology. More importantly, research experiences for graduate and undergraduate students allow them to experiment with their own potential, which can open new doors for professional and personal growth,” Maginnis says.

Contact: Sam Schipani, samantha.schipani@maine.edu