Ebola Virus Disrupts the Inner Blood-retinal Barrier by Induction of Vascular Endothelial Growth Factor in Pericytes

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2023 Jan 18

PMID 36652443

Authors

Jiawang Gao

Zhengyuan Guo

Wei Li

Xiaowei Zhang

Xian-En Zhang

Zongqiang Cui

Affiliations

Soon will be listed here.

Abstract

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.

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