Ebola virus disrupts the inner blood-retinal barrier by induction of vascular endothelial growth factor in pericytes

Ebola virus (EBOV) causes severe hemorrhagic fever in humans with high mortality. In Ebola virus disease (EVD) survivors, EBOV persistence in the eyes may break through the inner blood-retinal barrier (iBRB), leading to ocular complications and EVD recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we used the in vitro iBRB model to simulate EBOV in retinal tissue and found that Ebola virus-like particles (EBO-VLPs) could disrupt the iBRB. Cytokine screening revealed that EBO-VLPs stimulate pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF downregulates claudin-1 to disrupt the iBRB. Ebola glycoprotein is crucial for VEGF stimulation and iBRB breakdown. Furthermore, EBO-VLPs caused iBRB breakdown by stimulating VEGF in rats. This study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EVD survivors. Author summaryEbola virus (EBOV) persistence in eyes has been frequently reported and has become an enormous international public health challenge. EBOV persistence in the eyes may break through the inner blood-retinal-barrier (iBRB), leading to ocular complications and EBOV recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we found that Ebola virus-like particles stimulate retinal pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF causes iBRB breakdown by disrupting the tight junction protein claudin-1. Ebola glycoprotein plays a key role in VEGF stimulation and iBRB breakdown. Our study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EBOV survivors.

Automated summary

Ebola virus disrupts the inner blood-retinal barrier (iBRB) by stimulating the release of vascular endothelial growth factor (VEGF) from retinal pericytes, leading to ocular complications and disease recurrence. This study provides a mechanistic insight into the virus's impact on the iBRB and offers potential strategies for treating Ebola virus persistence.