Computational modeling finds wide genetic variability in SARS-CoV-2 immune response

Thompson Lab

The paper “Human leukocyte antigen susceptibility map for SARS-CoV-2” published in the Journal of Virology is the School of Medicine’s Paper of the Month.

Principal investigator Reid Thompson, M.D., Ph.D., describes the project. Thompson is an assistant professor in the Department of Radiation Medicine and member of the Computational Biology Program.

What did you hope to learn by doing this work?

It is widely believed that individual genetic variation could alter antiviral immune responses. There are numerous prior studies supporting this idea across a diversity of viruses and contexts.  However, with the COVID-19 pandemic, we sought to explore the potential role of individual genetic variability using computer-based predictions so that we might better understand why some infected individuals were asymptomatic while others were intubated or worse.

What did you actually learn?

By mapping the potential ability of individual human leukocyte antigen (HLA) types to present pieces of the SARS-CoV-2 virus to the immune system, we uncovered a wide level of variability that confirms the potential for some individuals to mount a significantly weaker – or stronger – antiviral response compared to other individuals. This magnitude of variability across HLA types surprised us. At the time, we did not have any clinical data to directly validate our predictions among actual individuals infected with the virus, but we showed that our predictions were consistent with real-world clinical outcomes during the closely-related SARS epidemic.

Mary Wood
Mary Wood

What do these findings mean for the future?

We stress that our findings are based purely on computational predictions and should not directly influence clinical care in any way at this juncture. Nonetheless, we anticipate a growing emphasis on the role of genetic variability (especially HLA types) in modifying COVID-19 severity, and note the founding of several consortia and a growing list of publications focused on these phenomena.  We anticipate that HLA typing will be more tightly integrated with COVID-19 clinical trials and testing more broadly, and that it could help to guide future vaccination strategies when a vaccine does arrive.

“This manuscript speaks to the collaborative ethos of our faculty and scientists in the Computational Biology Program, and their ability to respond rapidly to the COVID-19 crisis,” said Mary Heinricher, Ph.D., associate dean of research, OHSU School of Medicine. “I was excited to see their approach to modeling the immune response to SARS-CoV-2 and will be watching to see how it applies in the clinical environment.”

This research was supported by the Sunlin & Priscilla Chou Foundation and a VA CSR&D Career Development Award (1IK2CX002049-01).

Citation

Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, Thompson RF. 2020. Human leukocyte antigen susceptibility map for severe acute respiratory syndrome coronavirus 2. J Virol 94:e00510-20. https://doi .org/10.1128/JVI.00510-20. 

Pictured above, clockwise from top left: Austin Nguyen, Reid Thompson, Abhinav Nellore, Benjamin Weeder, Julianne David, Sean Maden.

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