A new PLOS Pathogens study describes how dengue virus may cause blood vessel leakage. Researchers conducted a battery of tests to pin down the mechanism by which the virus causes this potentially fatal damage.
Dengue is a mosquito-borne viral disease thought to cause around 390 million infections per year. While over 75 percent of infections are not thought to manifest clinically, infection can sometimes cause dangerous leakage of fluid from blood vessels.
The viral protein NS1 had previously been identified as a likely culprit behind this leakage, but it was not clear if it caused damage by disrupting the protective glycocalyx barrier of blood vessels or by triggering release of immune cell proteins known as inflammatory cytokines. So Dustin Glasner and colleagues set out to distinguish between the mechanisms.
To test if NS1 causes leakage via an inflammatory cytokine pathway, the researchers blocked cytokine activity in human cells, and also exposed mice bred to have inhibited inflammatory cytokine activity to the protein. Separately, to test if NS1 instead acts by disrupting the glycocalyx barrier of blood vessels, they inhibited molecules involved in the glycocalyx disruption process in mice and human cells. They found that NS1 was still able to disrupt cell layers and cause leakage when inflammatory cytokines were inhibited, but could not cause leakage when glycocalyx disruption was prevented.
The research suggests that NS1 usually acts to disrupt the glycocalyx lining of blood vessels to cause leakage, identifying this pathway as a potential target in development of treatments for dengue.
Research Article: Glasner DR, Ratnasiri K, Puerta-Guardo H, Espinosa DA, Beatty PR, Harris E (2017) Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components. PLoS Pathog 13(11): e1006673.https://doi.org/10.1371/journal.ppat.1006673
Image Credit: Glasner et al., 2017