Transcytosis Involvement in Transport System and Endothelial Permeability of Vascular Leakage during Dengue Virus Infection

Abstract

The major role of endothelial cells is to maintain homeostasis of vascular permeability and to preserve the integrity of vascular vessels to prevent fluid leakage. Properly functioning endothelial cells promote physiological balance and stability for blood circulation and fluid components. A monolayer of endothelial cells has the ability to regulate paracellular and transcellular pathways for transport proteins, solutes, and fluid. In addition to the paracellular pathway, the transcellular pathway is another route of endothelial permeability that mediates vascular permeability under physiologic conditions. The transcellular pathway was found to be associated with an assortment of disease pathogeneses. The clinical manifestation of severe dengue infection in humans is vascular leakage and hemorrhagic diatheses. This review explores and describes the transcellular pathway, which is an alternate route of vascular permeability during dengue infection that corresponds with the pathologic finding of intact tight junction. This pathway may be the route of albumin transport that causes endothelial dysfunction during dengue virus infection.

Plectin is Required for Trans‐Endothelial Permeability: A Model of Plectin Dysfunction in Human Endothelial Cells After TNF‐α Treatment and Dengue Virus Infection

“…A recent study in plasma proteome using proteomics and cytokine profiling in dengue patients showed that an elevated level of IL‐1 RA, IL‐17, TNF‐α, MCP1‐MCAF, and MIP‐1β was observed only in the plasma of DHF patients . Previous studies of DENV2 infection on EA.hy926 cells reported transcellular transport to be affected rather than paracellular transport, whereas paracellular transport was observed to be profound in the cells treated with DENV2 and TNF‐α in the present study . This finding also supported our finding that the synergistic effect of DENV2 and TNF‐α plays a role in the dysfunction of human ECs.…”

Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)

“…TNF-α related apoptosis inducing ligand (TRAIL), a type II transmembrane protein belonging to the TNF superfamily, has been shown to contribute to the induction of apoptosis in several types of tumor or virus-infected cells [35,48,49]. Moreover, TNF-α has been shown to enhance vascular hyperpermeability in dengue hemorrhagic fever [27,50]. This study showed that TNF-α mRNA up-regulated in the persistent EEHV4-infected calves suggesting that during EEHV infection, TNF-α not only contributed to apoptosis of the EEHV-infected cells, but also enhanced transmigration of leukocytes out of the blood vessels.…”

Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry

“…Compared to peripheral tissues, the rate of transcytosis at the BBB is unusually low. However, this rate may be augmented by increased Src kinase activity, which is mediated by a group of pathological and nonpathological stimuli, including inflammatory mediators and immune cell interactions with brain endothelium (41). Viruses may also increase vesicular trafficking, as has been observed in peripherally derived endothelial cells exposed to dengue virus (42).…”