A team including researchers from Seattle’s Benaroya Research Institute at Virginia Mason has identified a new pathway for protecting cells from deadly viruses — including the coronavirus that causes COVID-19 as well as the Ebola virus.
The technique, described in this week’s issue of the journal Science, takes advantage of a screening technique for seeking out new genes that can prevent infection.
In the newly published study, the research team pinpoints two genes that have already been the subject of biomedical studies. One gene is called the MHC class II transactivator, or CIITA. The second gene is known as CD74 — specifically, a variant known as p41.
Those genes have previously been thought to be involved in conventional immune responses involving T cells and B cells. The new findings, resulting from a screening technique called transposon-mediated gene activation, shed light on a different way in which the genes block infection.
The researchers found that CIITA can induce resistance in human cell lines by activating CD74 p41, which in turn disrupts the processing of proteins on the coat of the Ebola virus protein. That stops the virus from being able to infect its target cell. The same process blocks the entry pathway for an assortment of coronaviruses — including the SARS-CoV-2 virus that’s behind the current pandemic.
“Uncovering these new cellular protection pathways is incredibly important for understanding how we disrupt or change the virus infection cycle to elicit better protection against viruses like Ebola or SARS-CoV-2.” senior study author Adam Lacy-Hulbert, principal investigator at the Benaroya Research Institute, said in a news release. “And our new strategy helps us find mechanisms that have eluded conventional genetic screens.”
The strategy could lead to new therapies that work by blocking the activity of cathepsin proteases. “Many viruses, including coronaviruses, use cathepsin proteases to help them infect cells. … Thus, this antiviral mechanism has evolved to work against many different viruses,” said Case Western Reserve University’s Anna Bruchez, the study’s lead author.
Study co-author Lynda Stuart, deputy director for vaccines and human immunobiology at the Bill & Melinda Gates Foundation, said the new screening technique could fill gaps in scientists’ knowledge about the cellular mechanisms that block viral infections.
“We really need therapies that can block all viruses, including unknown future pathogens,” Stuart said. “To do that, we need to find common pathways that viruses target, and then develop approaches to block those vulnerabilities. Our work demonstrates one way in which cells can be modified to do this.”
In addition to Bruchez, Stuart and Lacy-Hulbert, the authors of the Science study, “MHC Class II Transactivator CIITA Induces Cell Resistance to Ebola Virus and SARS-like Coronaviruses,” include Ky Sha, Joshua Johnson, Li Chen, Caroline Stefani, Hannah McConnell, Lea Gaucherand, Rachel Prins, Kenneth Matreyek, Adam Hume, Elke Mühlberger, Emmett Schmidt and Gene Olinger.