In the high-stakes battle against viruses, some of the most crucial soldiers have fur, feathers, and snouts.
When SARS-CoV-2 emerged in 2019, scientists faced a race against time to understand this new threat. While petri dishes and computers provided some clues, researchers needed to answer critical questions that only living systems could address: How does the virus spread? What damage does it cause deep in the lungs? Which vaccines actually work? This crucial knowledge came not from humans, but from animals—specifically, Syrian golden hamsters.
These unassuming creatures became invaluable in COVID-19 research, revealing key insights about transmission and protection 9 . Their story exemplifies a fundamental truth in virology: when confronting viral threats, animal models serve as our indispensable allies, bridging the gap between cell cultures and human patients.
They are the unsung heroes in a battle that spans decades, from influenza and HIV to Ebola and beyond.
Animal models enabled quick evaluation of COVID-19 vaccines and treatments during the pandemic
Essential for establishing the safety of potential therapeutics before human trials
Reveal how viruses cause disease and spread within a living organism
Imagine trying to understand a complex society by studying isolated individuals in empty rooms. This resembles the limitation of cell culture models, where viruses interact with single layers of cells in laboratory dishes. While these systems reveal important aspects of viral entry and replication, they cannot show how an infection spreads through a living body, how the immune system mounts a defense, or why some infections turn deadly.
"Cell culture models have limitations, in that they do not allow the evaluation of virus tissue tropism, virus spread and pathogenesis in the host, or the host immune response to infection" 1 .
Animal models become essential because they possess what petri dishes lack—the incredible complexity of a whole biological system. They allow scientists to study the natural history of infection from initial exposure through spread within the host, the development of clinical signs, and finally, recovery or death 1 .
Perhaps most importantly, animal models are required for establishing the efficacy and safety of potential antiviral therapeutics and vaccines before human trials can begin 2 . They provide the critical evidence that an intervention might work—or fail—in a living organism.
Just as different tools serve different purposes in a toolbox, virologists select from various animal models based on the specific research question. The most common species each offer unique advantages—and limitations.
| Animal Model | Key Advantages | Common Applications | Limitations |
|---|---|---|---|
| Mice | Low cost, extensive genetic tools, well-characterized immune system | HIV, influenza, herpesviruses, SARS-CoV-2 (transgenic) | Not naturally susceptible to many human viruses 2 9 |
| Hamsters | Naturally susceptible to many viruses, develop human-like pathology | SARS-CoV-2, influenza, hemorrhagic fever viruses | Limited genetic and immunologic reagents 1 9 |
| Ferrets | Naturally susceptible to human respiratory viruses, display similar symptoms | Influenza transmission, SARS-CoV-2 transmission 6 9 | More expensive, require specialized care |
| Non-Human Primates | Close genetic and physiological similarity to humans | HIV/SIV, Ebola, SARS-CoV-2, hepatitis | Extremely high cost, ethical concerns 2 6 |
| Guinea Pigs | Recapitulate human pathology for several viruses | Respiratory viruses, arenaviruses, filoviruses 2 | Fewer commercial reagents available |
"When choosing an animal model for a study, factors to be considered include host susceptibility to the infection, animal size, cost, availability of housing and reagents, potential confounding coinfections, and ethical restrictions" 2 .
When SARS-CoV-2 emerged, the scientific community needed to quickly understand how this novel virus spread and how to stop it. Golden hamsters emerged as an unexpectedly perfect model, leading to a landmark experiment that demonstrated the effectiveness of face masks in preventing transmission.
In this elegantly designed study, researchers led by Chan et al. (2020) created a setup to test whether surgical mask partitions could reduce non-contact transmission between infected and healthy hamsters 9 .
Healthy hamsters were first inoculated with SARS-CoV-2 to create "index" (infected) animals.
Each infected hamster was placed in a cage adjacent to a healthy hamster, with an airflow system allowing air to pass from the infected animal's cage to the healthy animal's cage.
Between some cages, researchers placed a surgical mask material partition in the airflow path; other cages had no such barrier.
Researchers tracked infection in healthy animals by checking for viral load and antibody responses after exposure.
The findings from this hamster study provided crucial early evidence for public health interventions that would eventually become standard worldwide.
| Experimental Condition | Transmission Rate | Viral Load | Clinical Signs |
|---|---|---|---|
| No mask barrier | 66.7% (4/6) | High | Significant weight loss (≥10%) |
| Surgical mask partition | 25% (3/12) | Low to undetectable | No significant weight loss |
Perhaps most significantly, the study demonstrated that when mask partitions were used, infected animals also showed reduced viral shedding—suggesting that masks might protect both the wearer and those around them 9 . This two-way protection would become a cornerstone of public health messaging during the pandemic.
| Animal Model | Clinical Signs | Viral Replication Sites | Lung Pathology | Transmission Studies |
|---|---|---|---|---|
| Golden Hamster | Weight loss, lethargy, ruffled fur | Nasal turbinate (highest), lungs | Moderate to severe, resolves by day 14 | Highly efficient 9 |
| K18-hACE2 Mouse | Lethal infection, respiratory manifestations | Lungs, brain (in lethal cases) | Moderate to severe, progresses | Limited efficiency 9 |
| Ferrets | Elevated body temperature, reduced activity | Primarily upper respiratory tract | Mild immune cell infiltration | Highly efficient 9 |
Behind every successful virology experiment lies an array of specialized research reagents. These tools enable scientists to ask precise questions about viral behavior and host responses.
Synthetic compound that mimics viral RNA, stimulating immune response through TLR3 pathway. Used as prophylactic treatment to enhance antiviral defense 1 .
Drugs that modulate immune response to reduce inflammation-related tissue damage. Evaluated for preventing cytokine storm in severe viral infections 3 .
Laboratory-made antibodies that block virus from entering cells. Used as potential therapeutics and to measure vaccine efficacy 9 .
Hormone used to synchronize reproductive cycles in female animal models. Prepares female mice for intravaginal HSV-2 challenge studies 8 .
These reagents, combined with sophisticated animal models, create a powerful platform for uncovering viral secrets and developing countermeasures. From understanding how herpes simplex virus establishes latency in mouse models 8 to testing new vaccine candidates against emerging threats like Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) 3 , this toolkit continues to expand and evolve.
While animal models remain indispensable, the field continues to evolve with exciting technological advances. Researchers acknowledge that "no single animal model can fully replicate all key features of human herpesvirus-associated diseases," 8 and this principle applies to many viral pathogens.
These specialized models have become increasingly sophisticated, allowing researchers to create "humanized" mice with components of the human immune system. These models have enabled studies of viruses like HIV, Epstein-Barr virus, and human cytomegalovirus that were previously difficult or impossible to study in animals 6 .
Organoids are three-dimensional, stem cell-derived structures replicating human tissues' architecture and functionality—present a groundbreaking alternative , particularly for viruses that exhibit strict human tropism.
"Organoids are three-dimensional, stem cell-derived structures replicating human tissues' architecture and functionality—present a groundbreaking alternative," particularly for viruses that exhibit strict human tropism.
These miniature organ models have already demonstrated their value in studying viruses like Zika virus, where brain organoids revealed the virus's preference for infecting neural progenitor cells, explaining its link to microcephaly . Similarly, liver organoids have furthered our understanding of hepatitis B virus infection and replication .
Nevertheless, experts emphasize that organoids and traditional animal models will likely coexist rather than replace one another. While organoids excel at revealing tissue-specific responses, they cannot yet replicate the systemic immunity and complex organ interactions of a whole living organism . The future lies in selecting the right tool for the right question—and sometimes, that tool still has a heartbeat.
From the hamsters that helped us understand COVID-19 transmission to the mice that revealed how herpes viruses hide in nerve cells, animal models continue to be cornerstones of virology research. They are the bridge between theoretical knowledge and practical solutions, between laboratory discoveries and lives saved.
These models have contributed to nearly every major advance in fighting viral diseases—from antiviral therapies that stop viral replication to vaccines that train our immune systems for future battles.
"Almost every advance in medical science in the twentieth century, from antibiotics and vaccines to antidepressant drugs and organ transplants, has been achieved either directly or indirectly through the use of animals as models of disease," 4 .
The next time you hear about a breakthrough in viral research, remember that it likely depended on these unseen allies—the animals that stand between us and the microscopic threats we face together. Their contribution moves us closer to a world where pandemics are preventable, treatable, and ultimately, consigned to history.