One Universal Antiviral to Rule Them All?

Summary

For a few dozen people in the world, the downside of living with a rare immune condition comes with a surprising superpower—the ability to fight off all viruses. Columbia immunologist Dusan Bogunovic discovered the individuals’ antiviral powers about 15 years ago, soon after he identified the genetic mutation that causes the condition. At first, the condition only seemed to increase vulnerability to some bacterial infections. But as more patients were identified, its unexpected antiviral benefits became apparent. Bogunovic, a professor of pediatric immunology at Columbia University’s Vagelos College of Physicians and Surgeons, soon learned that everyone with the mutation, which causes a deficiency in an immune regulator called ISG15, has mild, but persistent systemic inflammation. “The type of inflammation they had was antiviral, and that’s when it dawned on me that these individuals could be hiding something,” Bogunovic recalls. When he and his colleagues looked at the individuals’ immune cells, they could see encounters with all sorts of viruses—flu, measles, mumps, chickenpox. But the patients had never reported any overt signs of infection or illness. “In the back of my mind, I kept thinking that if we could produce this type of light immune activation in other people, we could protect them from just about any virus,” Bogunovic says. Today, Bogunovic is closing in on a therapeutic strategy that could provide that broad-spectrum protection against viruses and become an important weapon in next pandemic. In his latest study, published Aug. 13 in Science Translational Medicine, Bogunovic and his team report that an experimental therapy they’ve developed temporarily gives recipients (hamsters and mice, so far) the same antiviral superpower as people with ISG15 deficiency. When administered prophylactically into the animals' lungs via a nasal drip, the therapy prevented viral replication of influenza and SARS-CoV-2 viruses and lessened disease severity. In cell cultu...