What makes a virus capable of causing a pandemic?

In a world still grappling with the COVID-19 pandemic, understanding where and how such an outbreak could occur again is crucial.

A new study uncovers some of the mysteries surrounding pandemic outbreaks based on two bat coronaviruses from Laos. These bat viruses, despite being genetically similar to SARS-CoV-2, appear to be poor at human transmission.

The investigation was conducted by a team of researchers at Yale University. Study lead author Mario Peña-Hernández, a Ph.D. student under the guidance of Akiko Iwasaki and Craig Wilen, made quite the revealing observation.

“These bat strains are 97% identical to SARS-CoV-2 genetically. We thought their phenotypic behavior would be similar. But we found that wasn’t true,” said Peña-Hernández.

Understanding viruses and pandemics

But, what exactly makes a virus capable of causing a pandemic? Well, it needs to transmit between people, enter human cells, evade the body’s defense systems, and cause disease.

SARS-CoV-2, the culprit of the COVID-19 pandemic, ticked all these boxes efficiently. Yet, it remains unclear why it succeeded so well while these genetically similar bat viruses struggle.

The bat viruses studied were able to enter some human cells efficiently and even outperform SARS-CoV-2 in evading defense systems.

However, they didn’t spread well between hamsters and caused only mild disease in mice. “We cannot tell from genomes alone what virus strains have pandemic potential,” explained Peña-Hernández.

Study synopsis

Iwasaki, a professor of Immunobiology at Yale School of Medicine (YSM), and Wilen, an associate professor at YSM, joined a team of researchers testing how well the two bat viruses infected human respiratory tract cells and rodents.

The findings suggest that despite efficiently infecting cells from the human bronchus, these viruses didn’t replicate well in cells from the nose.

“Innate immunity is particularly important against novel viruses to which people may have no adaptive immunity,” stated Iwasaki. The researchers found that the two bat viruses could evade certain innate immunity molecules.

Yet, despite their ability to infect airway cells and dodge defenses, these viruses still failed to transmit between animals.

“SARS-CoV-2 could evade innate immunity and transmit, so this suggested to us that these bat coronaviruses lack something that SARS-CoV-2 has,” Wilen noted.

Bat virus causing a pandemic

One thing the bat viruses lack is a “furin cleavage site.” A spike protein of the SARS-CoV-2 virus can be cut by an enzyme called furin, enabling the virus to efficiently enter human cells.

Without this cleavage site, the bat coronaviruses and mutated versions of SARS-CoV-2 didn’t replicate as well in nasal cells and were quickly outcompeted by viruses that had them in hamsters.

The presence of a cleavage site could be a key feature to look for in potential viral threats. However, there are likely other features that influence a virus’ transmission or disease-causing potential as well. How well a virus replicates in nasal cells may serve as a proxy for assessing its transmission capacity.

Pandemic preparedness strategies

As researchers continue to unravel the complexities of viral transmission, the insights gained from these bat coronaviruses can significantly inform pandemic preparedness strategies.

Understanding the unique traits that enable certain viruses, like SARS-CoV-2, to effectively infect humans and spread widely can help public health officials better anticipate and thwart future outbreaks.

These findings might steer efforts towards monitoring and studying viral pathogens more closely, particularly those lacking specific traits that correlate with pandemic potential.

Future research directions

Looking ahead, the study opens avenues for further research that could identify additional genetic factors influencing a virus’s ability to spread in human populations.

Researchers may explore how various environmental conditions, host interactions, and genetic mutations contribute to the emergence of new viral threats.

This continued investigation is essential not only for identifying potential zoonotic viruses but also for developing targeted vaccines and therapeutics that can mitigate the risk of future pandemics.

Future implications

From this study, it is clear that, although the bat viruses pose a modest threat, small genetic changes could significantly increase their pandemic risk. But the good news? Immunity against SARS-CoV-2 appears to neutralize these viruses. However, the quest to understand and pre-emptively prepare for future viral threats continues.

“Understanding whether viruses have the potential to transmit between humans is important,” said Iwasaki.

“If we find a virus that is transmissible and distinct enough from SARS-CoV-2 that we don’t have immunity against it, then we could create vaccines and strategies to combat it. We could have a head start.”

The study is published in the journal Nature Microbiology.

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