Bats, the only flying mammals, have long fascinated scientists for their unique characteristics.1 One of these is their ability to harbor viruses like Nipah, Ebola, and coronaviruses—which cause diseases in humans—without showing any signs of illness. Many researchers study why these viruses do not make bats sick, hoping to leverage this knowledge to develop better antiviral therapies. One of the hypotheses is that bat cells respond to viral infection in a different manner than human cells do.
“The only way we're going to learn where the differences are is if we actually have those cells in culture,” said Michael Letko, a virologist at Washington State University. However, scientists’ investigations are limited by the lack of access to stable bat cell lines, he said. While a few groups have generated cell lines, these are not as easily available for others to use.
Letko and his colleagues recently developed new bat cell lines from the tissues of a Seba’s short-tailed bat, which houses hantaviruses that can infect humans, and studied their antiviral responses.2 Their approach, published in PLoS Biology, offers a resource to study virus-host interactions in bats and a framework to develop these in vitro tools. The researchers have deposited these cell lines in a repository at the National Institutes of Health for public use.
“This is an exceptional article and a really excellent piece of work,” said Cara Brook, a disease ecologist studying bats as reservoirs for viruses at the University of Chicago, who was not associated with the study. “It [provides] a really excellent blueprint to the field for how to undertake these studies in a variety of different bat systems.”
To establish bat cell lines, Letko and his team isolated and cultured cells from different tissues of a Seba’s short-tailed bat. They then tried various methods to immortalize the cells, including overexpressing telomerase to reduce DNA damage from continuous cell division, knocking out the tumor suppressor TP53, and treating cells with viral proteins to turn off inhibition of cell division. These approaches yielded 11 different cell lines.
Next, the researchers focused on another aspect. “We wanted to make cells that would be useful for the community to study virus interactions,” said Arinjay Banerjee, a virologist at the University of Saskatchewan, and study coauthor. This required the cells to permit viruses to infect them and recognize and build an immune response against the viral antigens, he explained.
The team painstakingly treated all of their 11 cell lines with components of coronaviruses and filoviruses to investigate whether they permitted infection. While some cell lines allowed viral entry, they lost this capacity after repeated culturing, rendering them unfit for further experiments.
“Every time we saw something that looked like it was working, the question was, ‘Okay, well, how long is it going to stay like that?’,” recalled Letko. Finally, the researchers identified that cell lines derived from the bat’s kidneys were ideal: They permitted infection with both live hantavirus and viral components, and responded to them by increasing the expression of some genes encoding viral cytokines.
“They do a fine job of very carefully testing different mechanisms of immortalization and a whole suite of different viruses for virus entry,” said Brook. Although this offers an in vitro system to study virus-host interactions, she added that, “Work in tissue culture is always a bit divorced from the reality of the immune response in the natural host.”
Letko agreed, noting that the team next aims to derive organoids from bat tissues to capture a more physiologically relevant system. Banerjee added that although they only looked at cells from one bat species, the team is already replicating their protocol to derive cell lines from other species. “This is just the starting step.”
- Irving AT, et al. Lessons from the host defences of bats, a unique viral reservoir. Nature. 2021;589(7842):363-370.
- Gonzalez V, et al. Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses. PLoS Biol. 2025;23(4):e3003098.
