First human coronavirus isolated at UChicago more than 50 years ago

CoV-229E virus particles.

The virus that causes COVID-19 is new, but other coronaviruses have been around for decades. The first description of a coronavirus as a human pathogen occurred more than half a century ago at The University of Chicago.

This isn’t just an interesting historical footnote. As the COVID-19 pandemic continues to affect the global community and scientific researchers work to develop treatments and ultimately, a vaccine, they are building on knowledge pulled from research on other human coronaviruses (HCoVs) that are genetically related.

In 1962, University of Chicago researchers isolated a previously unidentified RNA virus during a study of upper respiratory infections among medical students. The researchers characterized this new virus and named it 229E (later HCoV-229E). The initial work, published in 1966 in Experimental Biology and Medicine, and the 1967 follow-up study in the Journal of Virology were able to give initial information on the growth times, virus size and images of the virus particle infection within human cells cultured in a dish. Researchers showed that this new virus did not react to antisera, blood serum containing antibodies, for any major known viruses, such as influenza strains, measles or mumps.

A similar study from the National Institutes of Health (NIH) in 1967 then confirmed multiple other strains of this new group of viruses shortly thereafter. This combination of work from UChicago and NIH defined a new group of viruses: human coronaviruses.

Until the 2003 outbreak of severe acute respiratory syndrome (SARS), human coronaviruses were associated with the mild symptoms of the common cold. Yet scientists continued to study them, and this work would prove valuable to the research needed to combat SARS. The genomes of two cold viruses — HCoV-229E and HCoV-OC43 — aided the development of early coronavirus tests used for respiratory infections. These tests were able to be used and refined as a beginning point for testing when SARS emerged as a novel virus, and now have been adapted for SARS-CoV-2, the virus that causes COVID-19.

“From a technical point of view, many assays are easily adaptable,” said Glenn Randall, PhD, Professor of Microbiology at the University of Chicago, who studies RNA viruses. “In our current research on COVID-19, we were able to get our virus assays working in one week because they had already been developed for other strains.”

Research on the mild coronavirus strains led to the identification of the family of host receptors (proteins on the surface of human cells) many strains of coronavirus use to infect cells. These receptors are in a family of proteins known as zinc metalloproteases — proteins that require a zinc metal molecule to perform their function. In 2003, decade-old research on HCoV-229E and other coronavirus host receptors allowed for the fast identification of the ACE-2 receptor as the host receptor needed for SARS-CoV infection. This receptor has now also been identified as the same receptor used for host cell infection in COVID-19.

‘We are lucky in some ways that SARS-CoV and SARS-CoV2 are quite similar,” Randall said. “We are not working in the dark”.

Randall and Dominique Missiakis, PhD, Professor of Microbiology, are leaders of a core facility at the Howard T. Ricketts Laboratory dedicated to SARS-CoV-2 research projects requiring Biosafety Level 3 containment. The Ricketts Laboratory is a regional biocontainment facility at Argonne National Laboratory, and is managed by the University of Chicago and the Biological Sciences Division.

“Prior knowledge is really guiding much of our response right now in many ways.” Randall said. “All of the vaccines in current clinical trials are based on delivery platforms that have already been tested for other disease models. The only thing new is the addition of the SARS-CoV-2 Spike protein to them.

Advances in sequencing technology also have helped track the outbreak. “Evidence is emerging that the virus might have picked up a mutation in Spike that allowed for better spread,” Randall said. “We also know from sequencing that the majority of Americans were infected by virus that came from Europe to New York and then disseminated.’

By performing upper respiratory infection studies in the 1960s, both University of Chicago and the National Institute of Health were able to begin an era of research into human coronaviruses that have provided scientists with a groundwork for ongoing COVID-19 research today.