To date, the current Ebola outbreak has seen 14,413 confirmed cases across the globe and 5,177 deaths from the disease. There is no vaccine or approved treatment for the virus, but scientists believe that finding out more about what the virus does inside the human body will bring us closer. In a new study published in PLOS Pathogens, researchers say they may have discovered how the Ebola virus causes severe inflammation and reduced blood vessel integrity.
The Ebola virus (EBOV) consists of seven genes. In their study, the investigators – including Viktor Volchkov of the Claude Bernard University of Lyon, France – focus on one of these genes, called glycoprotein (GP).
The team explains that GP expresses two proteins: shed GP and non-structural secreted glycoprotein (sGP). Shed GP is described as longer protein that covers the viral wall and protrudes from its surface, while sGP is a shorter protein that is secreted from the virus.
According to the researchers, both of these proteins are found at very high levels in the blood of humans and animals infected with EBOV. The team set out to determine what role these proteins play during infection.
To reach their findings, Volchkov and colleagues cultured shed GP and sGP in tissue before introducing them to human cells and monitoring their effects.
From this, they discovered that shed GP – but not sGP – can attach to macrophages and dendritic cells, which are types of immune cells. The researchers say that both of these cell types are targeted by EBOV during infection.
When the shed GP attaches to the immune cells, the cells begin secreting large amounts of pro-inflammatory and anti-inflammatory cytokines. Both shed GP and cytokines are able to travel in the bloodstream. This entire process may lead to an overactive immune response and cause fever, severe inflammation and septic shock in Ebola patients, the team says.
What is more, they found that the effect shed GP has on the immune cells is dependent on a molecule called TLR-4. When the researchers blocked TLR-4 with certain antibodies before the shed GP attached to immune cells, they found that the cells had a weaker reaction and secreted very few cytokines.
Further analysis revealed that shed GP affects the function of endothelial cells, which line the inside of the blood vessels. Through binding to immune cells and secreting cytokines, and through a direct mechanism, shed GP is able to increase the permeability of endothelial cells. This increased permeability may lead to the blood vessel leakage found in Ebola patients.
Commenting on their findings, the researchers say:
“Overall, our data contribute to a better understanding of the way EBOV might provoke the excessive cytokine storm that appears to be detrimental to survival of infection and provide new insights with which to develop therapeutic strategies to combat this newly defined role for shed GP in high viral pathogenicity.
In this regard, it is intriguing to speculate that treatment with anti-TLR4 antibodies could be used to reduce the inflammatory reaction caused by shed GP […]. Similarly, it is conceivable that neutralizing antibodies targeting shed GP could also help to alleviate the systemic shock-like syndrome seen with EBOV infection.”
The researchers note, however, that further studies looking at the association between shed GP and EBOV are warranted.
Earlier this month, Medical News Today reported on a study detailing the development of an Ebola vaccine that can be inhaled, which has shown promise in animal trials.