In June of 2020, yet another deadly Ebola outbreak was reported in the Democratic Republic of the Congo - the 11th outbreak since the virus was first discovered in the mid-1970s. Ebola virus sits at the top of the list of the world’s deadliest viral pathogens which leaves its victims fighting for their lives with symptoms such as fever, diarrhea, and internal hemorrhaging. In a bid to control ongoing outbreaks of the disease, scientists are on the hunt for targeted and effective antiviral therapeutics.
Many of Ebola’s devastating effects are known to be due to its manipulation of the body’s immune system which enables the virus to multiply and wreak havoc on internal organs. In a recent study published in the journal Cell, scientists take a journey into the genetics of Ebola’s effects on the immune system, one cell at a time.
Researchers from MIT’s Broad Institute used single-cell RNA sequencing technology to piece the puzzle together, starting with a sample of around 100,000 immune cells harvested from rhesus monkeys that had been infected with Ebola. The goal was to create a map of genetic activity in these immune cells at different stages of infection. This would pave the way for new Ebola therapeutics that target the immune system to alleviate symptoms.
Aaron Lin, co-first author of the study explained: “Treating the immune system in a more targeted way I think is where new therapeutics need to go.”
“Figuring out which branches of the immune system should be targeted can be informed by single-cell studies of infection and other kinds of analyses.”
The team found that a particular subset of immune cells called monocytes was most affected by Ebola infection, with the virus turning off key genes required to stimulate an effective immune response in these cells. Monocytes, a type of white blood cell, are the largest type of leukocyte and can differentiate into a variety of other immune cells including macrophages and myeloid lineage dendritic cells. Lin and team demonstrated how the virus downregulated genes relating to class II antigen presentation in monocytes, a process that triggers antibody production and triggers the activation of helper T cells. Moreover, Ebola choked the cells’ ability to synthesize interferon — an immune molecule that sets off a powerful antiviral response.
“Previous studies of Ebola virus in cells in a dish had generated hints of how the virus affects the immune system, but with more data across the whole genome and better resolution at a single-cell level from a natural infection over time, we got a more complete picture of what the immune system looks like during infection,” said Dylan Kotliar, a co-first author of the publication.