Why are some viruses harmless and others deadly? A.J. te Velthuis is on the case.

Posted on January 6, 2022

“AJ is the future of virology,” said Bonnie Bassler, the Squibb Professor in Molecular Biology and chair of the department. “Our department has always been a powerhouse in virology. When it was time to bring in a new assistant professor, our senior virologists — an incredible group of scholars and intellects — helped us understand where the future of this field is going, and they pinpointed him.”

“I work on RNA viruses, and I’ve been doing it for a very long time,” te Velthuis said. “I am particularly interested in why some new viruses, when they jump over to humans, suddenly trigger severe diseases, whereas when they were in bats or in other species, they seemed almost harmless.”

He studies the fundamental mechanisms for how viruses replicate and confuse our immune systems. He also works on new masks that inactivate viruses, antivirals that stop viral replication, and how variants of the same virus — such as Omicron or Delta — can arise and cause more harm than others. He pointed to the key role played by vaccination programs around the world.

“Unvaccinated people are acting as a reservoir from which the virus causing COVID-19 can keep jumping back into vaccinated people,” te Velthuis said. “It’s a perfect selection model for new variants, unfortunately.”

Defanging the coronavirus

In the earliest days of the pandemic, researchers experimented on live specimens of SARS-CoV-2, the virus that causes COVID-19, at great personal risk. Te Velthuis found a way to change that — to edit the genome of the new SARS strain so that he and his colleagues around the world could study the virus without exposing themselves and their loved ones to the deadly disease.

To do so, he took advantage of the fact that this is an unusually complex virus, with an elaborate blueprint coded in a long sequence of RNA (the single-stranded cousin of DNA).

The long genome can be thought of like a train, with a locomotive and a long string of cars linked together behind it. When the virus wants to give instructions to the cells it is invading, it needs to highlight the most relevant part of its genome, so it splices out that “train car” and reattaches it up front. The researchers in te Velthuis’ lab used that property to isolate one locomotive and one train car, resulting in a micro-virus that cannot infect new cells but can still be useful for testing antiviral treatments and studying new mutations.

“It’s not deadly anymore, because you need all the other ‘train cars’ to create a full, infectious virus particle,” te Velhuis said. “If you just have one train car in isolation, it can’t produce anything infectious, but it gives you information about how the wheels work, how strong the locomotive is.”