A study published in Cell Host & Microbe on May 13 reports that a single amino-acid change in a coronavirus protein can alter how the virus interacts with human and bat immune systems, influencing the risk of animal viruses adapting to humans. Researchers from the UCSF Quantitative Biosciences Institute, Icahn School of Medicine at Mount Sinai, Institut Pasteur, and Fred Hutchinson Cancer Center examined SARS-CoV-2 and a related bat coronavirus called RaTG13.
The team compared how each virus interacted with immune proteins in both bat and human lung cells. Their experiments used the first laboratory-grown lung cell line from the greater horseshoe bat. The focus was on a viral protein known as OrfB9. While SARS-CoV-2 and RaTG13 versions of OrfB9 differ by only one amino acid out of approximately 100, this difference significantly impacted immune responses.
In human cells, the SARS-CoV-2 version of OrfB9 disabled an immune alarm system, allowing the virus to multiply more effectively. In contrast, in bat cells, the RaTG13 version activated an immune protein that helped suppress viral replication.
Nevan J. Krogan, PhD, director of QBI and senior author of the study, said: "The difference between a virus that stays in bats and one that spills over into humans and causes catastrophic disease can come down to remarkably small genetic changes. By mapping these interactions at the protein level - across two viruses and two species - we can read the molecular signatures that predict spillover risk. It's the kind of early warning system the world needs."
