Single protein change may help bat coronaviruses adapt to humans
Researchers found that one amino-acid difference changed how related coronaviruses interacted with bat and human immune defenses.
By Tom Brennan · Health & Medicine Correspondent
3 min read
A single change in a coronavirus protein can alter how the virus behaves in bat and human lung cells, according to researchers from the University of California, San Francisco and partner institutions. The finding may help scientists identify animal viruses with a higher risk of adapting to people before they cause outbreaks.
The study, published in Cell Host & Microbe, compared SARS-CoV-2, the virus that causes COVID-19, with RaTG13, a closely related coronavirus found in bats that has not been known to infect humans. UCSF said the work focused on how viral proteins interact with immune proteins in cells from both species.
The research team included scientists from UCSF’s Quantitative Biosciences Institute, the Icahn School of Medicine at Mount Sinai, Institut Pasteur and Fred Hutchinson Cancer Center. According to UCSF, the study used the first lab-grown lung cell line developed from the greater horseshoe bat, allowing the researchers to compare infection-related responses across bat and human lung cells.
A small difference with broad effects
The researchers identified a viral protein called OrfB9 as a key point of difference between the two coronaviruses. UCSF said the OrfB9 versions in SARS-CoV-2 and RaTG13 are nearly the same, with only one amino acid differing among about 100 amino acids in the protein.
That small distinction was linked to sharply different immune effects in the experiments. In human lung cells, UCSF said, the SARS-CoV-2 version of OrfB9 suppressed an immune alarm system, helping the virus reproduce more effectively.
In bat lung cells, the RaTG13 version of the protein had the opposite kind of effect, according to the researchers. It activated an immune protein response that helped hold the virus in check.
The findings suggest that narrow genetic differences can change whether a coronavirus is contained in its usual animal host or gains traits that help it grow in human cells. The study does not say that a single mutation alone is enough to create a pandemic virus, but it shows how one protein change can reshape immune interactions across species.
Tracking spillover risk
UCSF said many pandemics begin when a pathogen moves from animals into people, and many scientists believe COVID-19 emerged through such a process. SARS-CoV-2 is closely related to coronaviruses found in bats, making bat-virus comparisons a major focus in research on future spillover risks.
Nevan J. Krogan, director of UCSF’s Quantitative Biosciences Institute and a senior author of the study, said the difference between a virus that remains in bats and one that spreads into humans can rest on very small genetic changes. He said mapping protein-level interactions across viruses and species could help reveal molecular signs of spillover risk.
The study was led by Jyoti Batra and colleagues, with funding from the National Institutes of Health, Howard Hughes Medical Institute, the Roddenberry Foundation, Gladstone Institutes, Fast Grants, the Innovative Genomics Institute, Chan Zuckerberg Biohub San Francisco and other supporters, according to UCSF.
By identifying the protein interactions tied to immune evasion and host adaptation, the researchers said scientists may be better able to flag animal viruses that deserve closer monitoring. The work adds molecular detail to the broader question of how viruses cross species barriers and become more dangerous to humans.
This story draws on original reporting from ScienceDaily.