Preventing the next pandemic

Humans are vastly outnumbered by viruses with the potential to do us harm. And yet, pandemics are relatively rare. What makes a particular virus capable of inflicting severe disease? That is a question that A.J. te Velthuis, an assistant professor of molecular biology who arrived at Princeton in early 2021, would very much like to answer.

“Why do these new viruses, when they jump over to us, suddenly become pathogenic, whereas when they were going around in bats or in other species, they seemed almost harmless?” te Velthuis asked.

His team has examined this question by comparing the seasonal flu virus H1N1 to two other viruses, the pandemic 1918 virus and the avian influenza virus H5N1. While seasonal flu usually causes mostly mild symptoms, the pandemic and avian flu viruses can trigger a severe reaction in which the lungs become filled with fluid. In 2018, te Velthuis and his team traced this immune system reaction to small bits of viral genetic material called mini viral RNAs.

When the COVID-19 pandemic hit, the question of how emerging viruses cause severe immune responses took on a special urgency. To study the SARS-CoV-2 virus without posing risk to human health, te Velthuis and his team, while still at Cambridge University, developed a version that cannot infect new cells. This weakened virus is useful for testing antivirals or studying new mutations.

The team is now working to discover how SARS-CoV-2 triggers the overreaction of the immune system that makes pandemic viruses so deadly. Finding the mechanism could inform the design of medicines that inactivate this process, transforming a severe health threat into a minor inconvenience.

“If we can have a tool, a drug for instance, that we can use when a pathogenic virus comes around, we can immediately turn it into a more manageable seasonal virus, and we wouldn’t see as much pressure on hospitals and other health-care institutes,” te Velthuis said. “That’s the bigger dream, the bigger goal.”