Maria Tokuyama, Assistant Professor in the UBC Department of Microbiology and Immunology, is a recent recipient of a Michael Smith Foundation for Health Research (MSFHR) Scholar Award. A competition for both scholars and research trainees, the scholar program supports early-career health researchers who are building leading-edge health research programs, training the next generation of scientists, and expanding their potential to make significant contributions to their field.

The MSFHR award is a salary award that will provide funds once a year over the span of five years, which the Tokuyama lab can apply to multiple projects in their research program. Specifically, Dr. Tokuyama’s research program will look at how endogenous retroviruses (ERVs) impact or influence immune responses.

ERVs are viral sequences that are major components of all human genomes, yet ERVs have been largely overlooked in the context of infectious diseases and chronic inflammation. Dr. Tokuyama hopes to fill this gap in knowledge through her research program that studies: 

Antiviral immunity against HSV-2

This project, which will overlap with funds from CIHR (Canadian Institutes of Health Research), is looking at the mechanisms of antiviral immunity against herpes simplex virus (HSV-2). Prior work from the lab has shown that in mice, ERVs are important in mediating protection against vaginal infection by HSV-2. Now, the lab is looking more mechanistically at how those endogenous retroviruses are providing protection against viral infection – starting with mice and then moving on to working with human samples with a UBC collaborator, Dr. Deborah Money (UBC OBGYN), who has collections of human vaginal swabs. More broadly, the lab is also looking at how ERVs influence vaginal epithelial health, which is an understudied area of health research that affects women’s health. By understanding how endogenous retroviruses modulate mucosal immunity, they hope to gain more insights into protective antiviral mechanisms against HSV-2 and other viruses.  

Inflammation during viral infection 

Inflammation is necessary to protect yourself from pathogens, but it can also be harmful if you have excessive inflammation. This is what happens in autoimmune diseases like arthritis, where there is too much inflammation in the joints, or lupus, where there is unwanted inflammation in many organs throughout the body. Existing treatments for autoimmune diseases are not very specific and leave patients immunosuppressed, which is why more work is needed to understand the different causes of autoimmune diseases to develop tailored treatments. Prior work has shown that endogenous retroviruses are dysregulated not only during viral infections but also in autoimmune diseases. We have shown that one of the endogenous retrovirus proteins is targeted by the immune system and can contribute to inflammation. Building on this, the lab is interested in understanding how these viral elements are impacting the severity or the degree to which our inflammatory responses are mounted during these in disease and how these viral elements influence individual differences in disease development and outcomes. 

Disease outcomes of COVID-19 

There is a wide range of disease outcomes with SARS-CoV-2 – many go about life asymptomatically or experience symptoms but fully recover, while others experience symptoms that are life-threatening that can lead to hospitalization or even death. So, what causes these differences in outcomes? One idea is that, potentially, endogenous retroviruses can modulate inflammation. Our lab has started to look at whether endogenous retrovirus expression in COVID-19 patients is different between individuals and seeing how that affects inflammation. Are there endogenous retroviruses that are expressed and track with better outcomes or with worse disease outcomes? We hope to be able to identify these elements and modulate their expression to either boost protection or reduce unwanted inflammatory consequences. 

With all these distinctive projects fitting under one big umbrella of research, the Tokuyama lab is trying to understand how endogenous retroviruses are impacting and modulating our immune system. Are they promoting antiviral immunity for beneficial consequences? Or are potentially contributing to detrimental inflammatory responses?

“We are starting to reveal how these endogenous retroviruses are affecting the immune system and have ideas of areas in which we can expand further,” shares Tokuyama. “But, more broadly, what they do, how they function, and how they intersect with known pathways and functionality of immune cells is really not known. People haven’t studied that. So, our research will hopefully also contribute towards our basic understanding of endogenous retrovirus biology.”