Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system

Abstract

The blood brain barrier consisting of astrocytes, pericytes and brain microvascular endothelial cells plays a vital role in the pathogenesis of neurotropic viruses by controlling the access of circulating molecules, immune cells or viruses into the central nervous system (CNS). However, this barrier is not impenetrable and neuroviruses have evolved to disrupt and evade it. This review aims to describe the underlying entry mechanisms of several neuroviruses such as (Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), Nipah virus (NiV), Rabies virus (RABV), Herpes simplex virus (HSV) and Human immunodeficiency virus (HIV)) into the CNS through BBB disruption. The mechanisms, through which neurotropic viruses enter the BBB, are being studied and are becoming clearer, however, some aspects still remain unknown. Some of these viruses are able to invade the brain parenchyma by a 'Trojan horse' mechanism, through diapedesis of infected immune cells that either cross the BBB paracellularly or transcellularly. Important mechanisms of BBB disruption associated with paracellular entry of viruses include alterations in expression or phosphorylation of tight junction proteins, disruption of the basal lamina and disruption of the actin cytoskeleton. In the absence of such mechanisms, indirect effects of viruses on the immune system are likely causes of barrier disruption.

Nervous system involvement after infection with COVID-19 and other coronaviruses

“…(Michalicova et al, 2017;Wright et al, 2008). Some viruses are neurotropic and can invade nervous tissues and cause infections of immune-functioning macrophages, microglia, or astrocytes in the CNS (Al-Obaidi et al, 2018;Soung and Klein, 2018).…”

The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in vitro models of the human blood–brain barrier

“…Viruses negatively affect the BBB not only by direct interaction with endothelial cells but also by induction of host immune responses that result in elevated expression of pro-inflammatory cytokines, chemokines, cell adhesion molecules that lead to a demise in BBB structural and functional integrity 49 . A disruption in the BBB facilitates crossing of viral particles and infected immune cells further elevating levels of inflammatory mediators [49][50][51][52] . SARS-CoV-2 could employ such mechanisms of neuroinvasion and future studies will help discern whether this is the case.…”

Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers

“…Another studied virus that is involved in encephalitis and BBB disruption is HIV, known to cause severe neurological disorders and leading to HIV-related encephalitis [109] since BBB is impermeable to 98% of antiretroviral drugs [110]. The possible mechanism responsible for BBB disruption in HIV-1 encephalitis is considered a "Trojan horse" mechanism, where HIV infects specific T-lymphocytes and circulating monocytes, then entering to CNS through BBB gaps and followed by inflammatory reactions [111], but, in the last years nanotechnology has been intensely explored and several experimental attempts have been carried out in order to enhance the BBB permeability toward antiretroviral drugs, briefly described below based on the nano-based formulation composition, since it is well known that the size and surface functionalization influence transport properties within tissues:…”