Bats are important animals that help maintain ecosystem balance and human well-being. They play key roles like pollinating plants, dispersing seeds, and controlling insect populations. But of late they have become popular for a different reason: their unique ability to harbour viruses without succumbing to disease.

SARS, MERS, Ebola, COVID-19 — some of the most devastating human diseases of the past century are believed to have originated in bats. Despite their central role in pandemic ecology, we know surprisingly little about how viruses interact with bat biology, or why some viruses remain harmless in bats but become deadly when they jump to humans.

Bat organoids

Studying bats has numerous challenges. They are nocturnal, elusive, and in many regions protected by law. Another challenge is a lack of suitable research tools and animal models. Traditional laboratory animals like mice or monkeys fail to replicate the unique physiological traits of bats and primary bat cells are notoriously hard to grow in culture.

Even cell lines derived from the same bat species that hosted a virus may not support its replication due to the loss of key host receptor expression.

In a study recently published in Science, an international team of researchers has developed the world’s most comprehensive platform of bat organoids: small, three-dimensional lab-grown tissues that replicate the structure and function of real bat organs. Organoids have long been developed and used for human biomedical research — and they are now being applied to bats.

Previous attempts at creating bat organoids were limited to a single fruit bat species and one organ type. These models failed to capture the full diversity of bat species, especially those found in temperate regions like East Asia, where many emerging viruses have been identified.

To address this, the team created organoids from five insect-eating bat species native to Asia and Europe. These included models of the trachea, lungs, kidneys, and intestines. These structures mimic the real tissues closely, with features like mucus-producing goblet cells and gas-exchanging alveoli.

When exposed to viruses like SARS-CoV-2, MERS-CoV, influenza A, and Seoul orthohantavirus, the organoids revealed species and organ-specific vulnerabilities. For example, MERS-CoV replicated easily in the respiratory organoids of several bat species. SARS-CoV-2, the virus responsible for COVID-19, surprisingly couldn’t infect any of the bat respiratory tissues unless researchers added a human gene, TMPRSS2, which enabled the virus to enter human cells.

This finding may help explain why some viruses may not initially pose a risk to humans but become dangerous after acquiring adaptations that allow them to survive and replicate in the human body.

In their study, the researchers also exploited the organoid platform’s usefulness for virus discovery. Using faecal samples from wild bats, they were able to isolate two previously unidentified viruses: a mammalian orthoreovirus and a paramyxovirus. The paramyxovirus wouldn’t grow in normal lab cells but flourished in the organoids, likely because it requires bat-specific cellular factors to enter and replicate but which are absent in conventional lab cell lines.

Immortal bat cell lines

In a separate study published in PLoS Biology, another group created immortalised bat cell lines from Seba’s short-tailed bat (Carollia perspicillata), a fruit bat native to Central and South America. These cell lines were developed from organs like the kidney, brain, liver, and spleen tissues, and were shown to support replication of MERS-CoV, vesicular stomatitis virus and Andes orthohantavirus, a close relative of deadly hantaviruses found in humans.

In their study, the researchers observed that the kidney cells permitted natural entry and replication of MERS-CoV whereas SARS-CoV-2 was unable to infect them — mirroring the results observed in the organoid models. Both bat cells and organoids activated immune responses when exposed to synthetic viral RNA or viruses, similar to real bats. 

Global virology resource

Together, these two new bat models demonstrate the ability to monitor real-time immune responses in bat tissues, offering an advanced tool to understand how bats coexist with viruses that are lethal to other species. While organoids let researchers study how viruses behave in real tissue, the cell lines allow high-throughput testing of viral entry and immune reactions.

Both initiatives aim to establish global biobanks of bat-derived organoids and cell lines to enhance pandemic preparedness. The Carollia perspicillata cell lines are already being distributed through ATCC, a major biological repository. Meanwhile, the organoid initiative plans to expand its reach by incorporating additional bat species and tissue types.

Together, these resources are expected to help researchers (i) track species-specific virus behaviour; (ii) identify immune pathways and viral entry points; (iii) screen antiviral drugs under more realistic conditions; (iv) predict zoonotic spill-over risk before outbreaks begin.

Implications for India

India is home to more than 120 bat species, with particularly high bat diversity in the Northeast and the Western Ghats. Despite this diversity, virological data on these bats is limited and many species are poorly studied. In the Northeast, studies have detected antibodies to Ebola and Marburg viruses in both bats and humans. Kerala has also experienced multiple Nipah virus outbreaks, with fruit bats identified as the likely carriers. Nonetheless, efforts to study native bats in depth are hindered by biosafety concerns, legal restrictions, and limited research infrastructure.

These new lab-grown models could offer a safer, more ethical way forward, allowing researchers to study bat viruses without handling live animals.

Given the ongoing pressures from habitat loss, climate change, and increased human-wildlife interactions, the risk of new zoonotic diseases is also rising. This prompted the Government of India to launch an inter-ministerial scientific initiative on April 4 to study these risks. Tools like bat organoids and cell lines could support more effective monitoring and research into emerging viruses and improve the country’s preparedness for the next pandemic.

Manjeera Gowravaram has a PhD in RNA biochemistry and works as a freelance science writer.