Ebola virus disrupts the inner blood-retinal barrier by induction of vascular endothelial growth factor in pericytes 2023 Gao et al

[Andy]

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.

Author summary
Ebola 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.

Open access, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011077

 

[Hutan]

EBOV persistence has been shown in immune-privileged sites, including the eyes, brain and testes [4–6]. Viral materials were detected in these immune-privileged sites in EVD survi- vors long after clinical recovery with no detectable viral material in blood or target organs [7]. EBOV persistence in immune-privileged sites also leads to EVD recurrence in some survivors [5]. This finding demonstrated that during persistence, EBOV can cross the blood-tissue bar- rier to enter the bloodstream from immune-privileged sites. EVD recurrence caused by the dissemination of EBOV from immune-privileged sites into the blood increases the risk of the initiation of new chains of viral transmission and causes an enormous international public health challenge [8–9].

EBOV persistence has been reported to cause various sequelae, such as arthralgia, cognitive impairment, headache, hearing loss, and myalgia, in a large number of EVD survivors [10]. Among them, approximately 35% of EVD survivors suffered from different kinds of ocular complications, including blurry vision, vitreous inflammation and optic neuropathy [11–12].

Post-Ebola syndrome is similar (perhaps the same? as) ME/CFS. Ebola persists in immune-privileged sites and cannot be identified from blood tests.

Our finding that EBO-VLPs induced VEGF secretion by pericytes revealed a new mechanism of iBRB break- down. Furthermore, we showed that Avastin, a VEGF neutralizing antibody, could reduce bar- rier dysfunction induced by EBO-VLPs administration. It is consistent with previous study that the barrier dysfunction of bovine retinal endothelial cells caused by VEGF could be restored by inhibiting VEGF [39,40]. Ocular anti-VEGF therapy has been shown to be an effective treatment for some retinal diseases [39].

An anti-VEGF medication was found to reduce barrier dysfunction (although presumably, if you don't eliminate the Ebola virus, the dysfunction would continue).

They give numerous examples of viruses affecting the integrity of vascular endothelium by various means.