What shapes a virus's pandemic potential? SARS-CoV-2 relatives yield clues

 Two of the closest known relatives to SARS-CoV-2 -- a pair of bat coronaviruses discovered by researchers in Laos -- may transmit poorly in people despite being genetically similar to the COVID-19-causing virus, a new Yale study reveals.

The findings -- published July 29 in the journal Nature Microbiology -- provide clues as to why some viruses have greater "pandemic potential" than others and how researchers might go about identifying those that do before they become widespread.

For a virus to cause a pandemic it needs to be able to transmit between people, enter human cells, evade the body's defense systems, and cause disease. SARS-CoV-2, the virus that precipitated the COVID-19 pandemic, has been able to do all of this. But it's not yet clear why it is so efficient.

"We don't know what makes a virus have pandemic potential," said Mario Peña-Hernández, a Yale Ph.D. student in the labs of Akiko Iwasaki and Craig Wilen and lead author of the study. "These bat strains are 97% identical to SARS-CoV-2 genetically and we thought that, because they are the virus's closest known relatives, their phenotypic behavior -- or the way they infect and cause disease -- would be similar to SARS-CoV-2. But we found that wasn't true."

While the bat coronaviruses were able to efficiently enter some human cells and evade defense systems (often better than SARS-CoV-2 does), they did not transmit, or spread, well between hamsters and caused more mild disease in mice.

"The findings show us that we cannot tell from genomes alone what virus strains have the capacity to create a pandemic," said Peña-Hernández.

Other authors included Iwasaki, Sterling Professor of Immunobiology at Yale School of Medicine (YSM) and professor of epidemiology (microbial diseases) at Yale School of Public Health, and Wilen, an associate professor of laboratory medicine and of immunobiology at YSM.

For the study, the researchers used copies of the two bat coronaviruses and tested how well they were able to infect lab-cultured human respiratory tract cells and rodents. The work was done under the university's highest standard of biosafety. (Specifically, it was conducted under what is characterized as biosafety level 3+, requirements for which include restricted lab access, specialized personal protective equipment and respirators, and for experiments to be performed in biocontainment cabinets in a negative pressure facility).

The researchers found that while the two bat coronaviruses were effective at infecting cells isolated from the human bronchus -- the airway that connects the trachea to the lung -- they did not replicate well in cells from the nose.

sources-science daily