A team including researchers from Seattle’s Benaroya Research Institute in 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, uses a screening technique to look for new genes that can prevent infection.
In the newly published study, the research team identified two genes that are already 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.
Of these genes, they have previously been thought to be involved in conventional immune responses with T cells and B cells. The new findings, as a result of a screening technique called transposon-mediated gene activation, shed light on another way in which the genes block infection.
The researchers found that CIITA can induce resistance in human cell lines by activating CD74 p41, which disrupts the processing of egg whites on the coat of the Ebola virus protein. This stops the virus from infecting its target. The same process is blocking the entry path for an assortment of coronaviruses – including the SARS-CoV-2 virus that is behind the current pandemic.
“Discovering these new cellular pathways is incredibly important in understanding how we disrupt or change the virus infection cycle in order to provide better protection against viruses such as Ebola or SARS-CoV-2.” senior student author Adam Lacy-Hulbert, lead researcher at the Benaroya Research Institute, said in a news release. “And our new strategy helps us find mechanisms that have escaped conventional genetic screens.”
The strategy may lead to new therapies that work by blocking the activity of cathepsin proteases. Many viruses, including coronaviruses, use cathepsin proteases to help infect cells. “Thus, this antiviral mechanism has evolved to work against many different viruses,” said Anna Bruchez, Case Western Reserve University, lead author of the study.
Study co-author Lynda Stuart, deputy director of vaccines and human immunobiology at the Bill & Melinda Gates Foundation, said the new screening technique could fill gaps in scientists’ knowledge of the cellular mechanisms that block viral infections.
“We really need therapies that can block all viruses, including unknown pathogens,” Stuart said. “To do that, we need to find common pathways that target viruses, and then develop approaches to block those vulnerabilities. Our work demonstrates one way cells can be adapted to do this. ”
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