Many of the fatal infectious diseases in humans have originated from bats. The viruses that caused the COVID-19 pandemic, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) all came from bats. However, since bats are wild animals that are difficult to handle in laboratories, there have been limitations in actually isolating or analyzing the viruses present in them.
Domestic researchers developed experimental tools to solve challenges in infectious disease research. Choi Young-ki, Director of the Virus Research Institute at the Institute for Basic Science (IBS), and Koo Bon-gyeong, Director General of the Genome Editing Research Group, noted on the 16th, "We created organoids, a mini-organ made of cells from Korean native bats, and cultivated and analyzed novel viruses within them." The results of this research were published that day in the international journal Science.
◇Wild bats realized as mini-organs
During a meeting at the IBS headquarters in Daejeon, Director Choi said, "Recently, we are seeing an increasing number of zoonotic diseases that are transmitted from animals to humans. Among them, bats have been identified as hosts of important pathogens that have caused pandemics."
Bats live 3 to 10 times longer than other mammals by weight. They also live in caves close together in the tens of thousands. The caves where bats reside serve as optimal culture rooms for viruses. There are 137 species of viruses found in bats, of which 61 are known to infect humans. Scientists expect that the so-called 'virus X,' which could trigger another pandemic following COVID-19, is likely to emerge from bats.
However, wild bats are difficult to catch, making experiments challenging. It was hard to secure enough tissue and the experimentation itself was complicated. Director General Koo stated, "Since we cannot use flying bats for every experiment, there was a need for a system to replicate bat organs in the laboratory."
The research team introduced organoid technology. Organoids are mini-organs created by culturing stem cells that can grow into all human cells in structures similar to those of organs. Previously, researchers had cultured human or animal cells in laboratories to grow pathogens or test drugs. Organoids are better at mimicking the in vivo environment than cells cultured on flat plates.
◇Bats' immune responses vary with viruses
The research team created bronchi, alveoli, small intestine, and kidney organoids from cells of five species of bats found in Korea and infected them with 10 types of bat viruses. There are few global cases of studying bat viruses in laboratories. Notably, the study encompassing various bat species and organs is unprecedented in scale, which is why Science paid attention to this research achievement.
The experimental results showed that the strength and patterns of immune responses varied significantly depending on the species of bats, organs, and types of viruses. This could provide vital clues to understanding how viruses spread within actual animal organs and how pathogenicity manifests. Director Choi remarked, "This is similar to the effect of researching multiple organs from a single animal."
The researchers also succeeded in cultivating and isolating two mutant viruses found in fecal samples from wild bats using organoids. Kim Hyun-jun, senior researcher at the New Virus Research Center and first author of the study, explained, "We managed to cultivate and isolate viruses that were difficult to amplify using conventional cell culture methods in a living state," adding that this will help quickly understand the characteristics of emerging viruses and expedite vaccine development.
◇Antiviral drugs and vaccines can also be tested
The significance of this study goes beyond simply cultivating viruses in mini-organs of bats. Researcher Kim Hyun-jun explained, "This can be utilized not only for the detection of new viruses but also for verifying the efficacy of antiviral agents and researching gene functions."
The research team tested the effects of antiviral drugs such as Remdesivir on mutant viruses derived from bats. They stated that using organoids allowed for more precise observation of the antiviral agents' infection inhibition effects than traditional cell experiments.
The research process was not smooth. Many bats in Korea are classified as natural monuments or protected species, making collection itself difficult. There was also a lack of genomic information, complicating analysis. Researcher Kim stated, "We encountered difficulties due to the lack of reference genomes, but we overcame them with a new analysis technique using similar species."
They also created the research tools from scratch. Director General Koo remarked, "Biotechnology tools developed for humans or mice do not work on bats, so we had to optimize the experimental conditions anew for each parameter," describing it as akin to "driving on an unpaved road for the first time." The researchers stated that close collaboration among IBS researchers helped overcome these challenges, with Director Koo adding, "Being in the same building, we naturally collaborated."
Starting with bat organoids, the research team is expanding the range of organoid experiments to various animal species. They are constructing small intestine organoids from various animals such as ferrets, chickens, cows, and primates, and plan to analyze interspecies transmission pathways of infectious diseases based on the characteristics of each organ.
Director Koo stated, "Zoonotic diseases do not typically jump directly from bats to humans; they often go through intermediate hosts," noting that organoids could simulate that pathway within the laboratory.
References
Science (2025), DOI: https://www.science.org/doi/10.1126/science.adt1438