The Scientist has some satisfying news to ring in the New Year. The same genetic mechanism that boosts immunity to one lethal pandemic – the hemorrhagic fever known as Ebola – also helps protect us against the coronavirus, giving hope for new therapies to prevent both diseases (and maybe more):
In the Ebola experiments, [Adam] Lacy-Hulbert, [Anna] Bruchez, and their colleagues [at the Benaroya Research Institute in Seattle] had been using a genetic screen called transposon-mediated gene activation to search for natural antiviral mechanisms within cultured human bone cancer cells. Transposons, mobile genetic elements found throughout the genome, can be added to cells to knock out genes they randomly insert into. The team had integrated a promoter sequence into the transposons so that, in addition to knocking out some genes, they would turn other genes on. After adding these transposons to flasks of human cells, Bruchez introduced viruses engineered to express an Ebola glycoprotein, killing most of the cells. The team genotyped the few cells that remained and discovered two genes that were crucial to the cells’ survival: NPC1 and CIITA.
One isoform in particular, p41, could keep CD74 knockout cells alive in the face of the virus with the Ebola glycoprotein.
The group found that p41 inhibited entry of SARS-CoV-2 into the cells as well. Lacy-Hulbert suggests that this pathway could trigger broad resistance to viruses and that this “might have been CIITA and CD74’s original role. Then that activity got co-opted into the adaptive immune system, which evolved later.”
You can read the (even more technical) research here, in Science.