HMN 2026: How Lab-grown airway organoids reveal viral infection in wildlife species

Experimental infections, where a pathogen is introduced into the host body to see its effects in action, are considered the gold standard for assessing how vulnerable a host is, offering clear insights into how a pathogen causes disease and spreads through populations. This approach requires deliberately infecting live animals, which not only raises clear ethical concerns but also often proves impractical for many wildlife species, especially endangered ones, where conservation efforts take precedence. Scientists have found a potential solution to this problem.

They developed a new method for growing miniature organs, called airway organoids, in the lab for 10 different animals, including wildlife such as the red panda and Goeldi’s monkey, as well as livestock.

They turned tissue samples from each animal into 3D airway models that recreate how the respiratory tract functions and is built at the cellular level, enabling researchers to test susceptibility to influenza viruses of both mammalian and avian origin.

Tests conducted using the organoids showed large differences in infection trends across animal species and in the extent of damage the virus causes in their cells. These results were consistent with what is already known from real-life infections and field studies.

The findings are published in Emerging Microbes & Infections.

Miniature organs, massive impact

Infectious diseases are threatening the lives of animals and humans while posing a serious threat to the food chain and the broader ecosystem.

Climate change and globalization have increased the risk of zoonotic spillovers, where infections spread from animals to humans, and when that happens, controlling the outbreak becomes rather difficult. To limit these outbreaks, it is important to know which animal species are susceptible and which may carry viruses without showing signs of disease.

Testing on live animals, although considered a gold standard, raises significant practical and ethical concerns, while in vitro tests using cultured cells often lack the cellular complexity and diversity found in real animal tissues.

For this study, researchers collected airway and lung tissues from eight mammals and two birds, ranging from common livestock such as pigs and chickens to wildlife such as the red panda and Iberian wolf. The isolated cells were embedded in ice-cold Matrigel, a gel-like scaffold that mimics the body’s natural extracellular environment.

Once the matrix solidified, lung expansion medium was added, and the cultures were incubated in a highly humid atmosphere at 37°C in 5% CO?, to support growth. Within a few weeks, the cells organized into spherical, cystic 3D organoids that mimicked the multicellular arrangement and function of the original airway tissue, including the presence of moving microscopic hairs called cilia.

The 3D structures were then carefully flattened into 2D sheets for the next step, which involved introducing two different types of Influenza A: pH1N1, which caused the 2009 pandemic flu, and H5N1, a dangerous avian flu. Once the organoid sheets were infected, researchers tracked infection rates, the number of cells that remained alive and healthy after infection, and changes in the virus over time.

They found that different animal organoids responded to the virus in unique ways. Some were more susceptible, while others were resistant. For instance, Iberian wolves and Dama gazelles were highly vulnerable to both the pandemic flu and the avian flu, while red pandas were susceptible only to the pandemic strain.

Goeldi’s monkeys showed high infection rates but little cell damage, suggesting they could act as silent carriers, spreading the virus without showing illness. These findings were consistent with known real-world data for some species.

The findings show that a single, standardized process for building mini-organs can unlock disease research across dozens of species, no live animal testing required. The researchers believe this new approach to studying infectious diseases could help our efforts to improve pandemic preparedness, disease surveillance at the animal–human interface, and wildlife conservation.

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