Viruses such as dengue virus (DENV), SARS-CoV-2, Ebola virus and others, can disrupt endothelial cell function and cause blood vessels to become leaky (vascular leak). This activity is linked to severe outcomes as it can lead to microclots (e.g. COVID blisters, long covid), hemorrhage (e.g. Ebola), multiorgan failure, and/or sepsis. Scott and others have discovered a novel class of viral protein encoded by these viruses termed “viral toxins” that interact with endothelial cells to mediate vascular leak. DENV NS1 and SARS-CoV-2 Spike are viral toxins that are released from infected cells and circulate in the blood of patients, interacting with endothelial cells resulting in the upregulation of enzymes that compromise barrier function (disruption of the glycocalyx layer and intercellular junctions). Scott’s work has begun to uncover mechanisms by which DENV NS1 and SARS-CoV-2 Spike trigger vascular leak through modulation of TGFbeta and adrenergic signaling pathways. Treatments with approved drugs targeting these pathways protect mice from lethal DENV and SARS-CoV-2l dengue challenges. Biering’s PAD-sponsored research will explore host signaling pathways required for viral toxin-triggered vascular leak for DENV, SARS-CoV-2, and other viruses. He will also test the efficacy of novel therapeutics that block virus-induced vascular leakage.
Picture provided by Scott Biering of Scott in his laboratory with postdoc Vasiliya Kril