Bats, nature’s only flying mammals, have captivated scientists for years, primarily due to their unique characteristics. One remarkable trait is their ability to host viruses such as Nipah, Ebola, and coronaviruses-pathogens capable of causing severe diseases in humans-without exhibiting any signs of illness. This phenomenon has spurred intense research into understanding why these viruses don’t harm bats, with the ultimate goal of developing more effective antiviral treatments for humans.

A leading hypothesis suggests that bat cells respond to viral infections differently than human cells. To investigate this, scientists need access to stable bat cell lines, which have been historically scarce.

the Challenge of Studying Bat Cells

The scarcity of readily available bat cell lines has significantly hampered research efforts. 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. While some research groups have managed to create cell lines, these resources are not widely accessible to the broader scientific community, limiting the scope of research.

Breakthrough: New Bat Cell Lines Developed

recently, Dr. Letko and his team achieved a meaningful breakthrough by developing new bat cell lines derived from the tissues of a Seba’s short-tailed bat. This bat species is known to carry hantaviruses, which can be transmitted to humans. The team’s research, published in plos Biology, details their approach to creating these cell lines and studying their antiviral responses. The cell lines have been deposited in a repository at the National Institutes of Health for public use, ensuring accessibility for researchers worldwide.

Expert Commentary

Cara Brook, a disease ecologist at the University of Chicago specializing in bats as viral reservoirs, lauded the work, stating:

This is an remarkable article and a really excellent piece of work. It [provides] a really excellent blueprint to the field for how to undertake these studies in a variety of different bat systems.
Cara Brook, University of Chicago

The Process of Creating Bat Cell Lines

Dr. Letko’s team meticulously isolated and cultured cells from various tissues of a Seba’s short-tailed bat.They then employed several methods to immortalize the cells, including:

• Overexpressing telomerase to minimize DNA damage from continuous cell division.
• Knocking out the tumor suppressor TP53.
• Treating cells with viral proteins to suppress cell division inhibition.

These efforts resulted in the creation of 11 distinct cell lines.

Ensuring Utility for Virus Interaction Studies

A key objective was to develop cell lines that would be valuable for studying virus interactions. Arinjay Banerjee, a virologist at the University of Saskatchewan and a coauthor of the study, explained:

We wanted to make cells that would be useful for the community to study virus interactions.
arinjay Banerjee, University of Saskatchewan

This required the cells to be susceptible to viral infection and capable of mounting an immune response against viral antigens.

Rigorous Testing and Identification of Ideal Cell Lines

The team subjected all 11 cell lines to components of coronaviruses and filoviruses to assess their susceptibility to infection. While some cell lines initially permitted viral entry, they lost this ability after repeated culturing.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?’ Dr. Letko recalled. Ultimately,kidney-derived cell lines proved to be the most suitable,allowing infection with both live hantavirus and viral components,and responding by increasing the expression of genes encoding viral cytokines.

limitations and Future Directions

While the new cell lines offer a valuable in vitro system for studying virus-host interactions, Dr. Brook noted:

Work in tissue culture is always a bit divorced from the reality of the immune response in the natural host.
Cara Brook, University of Chicago

Dr. Letko acknowledged this limitation, stating that the team’s next goal is to create organoids from bat tissues to better replicate a physiologically relevant system. Dr. Banerjee added that they are already applying their protocol to derive cell lines from other bat species, emphasizing that This is just the starting step.