How does herpes simplex virus hijack the retrograde transport machinery to infiltrate the brain and cross blood-brain barrier to deliver appropriate therapeutic for brain injuries.Is it reversing the tightness of occludins and Junction Adhesion protein constituting tight and adheren junctions or insulating trans-endothelial electrical resistance or some other reason.
Hi Prithvi,
Most blood vessels that enter the CNS are composed of non-fenestrated endothelial cells that use tight junctions to limit the movement of cells and molecules through inter-endothelial gaps. Endothelial cells also provide a physical acellular barrier to the perivascular space by producing a basement membrane consisting of laminin α4 and laminin α5. Astrocytes also contribute to the blood–brain barrier system by forming the glial limitans, a dense network of the basal lamina and astrocytic endfeet. Because astrocytes reside exclusively in the parenchyma, they do not contribute to meningeal or choroid plexus barriers, which are part of the blood–CSF barrier system. Meningeal blood vessels instead rely on non-fenestrated endothelium only, whereas choroid plexus blood vessels have normal fenestrated endothelium but are encased by a second layer of epithelial cells that provides some barrier protection. Although the blood–brain barrier and blood–CSF barrier are typically sufficient to shield the CNS from various insults, neurotropic viruses have evolved strategies to breach these barrier systems and enter the CNS. As your question related to herpes simplex virus (HSV), it was shown to enter the brain amygdala and hippocampus through the olfactory nerve and locus coeruleus. This DNA virus has the tendency to enter latency within the CNS. In the infected murine model, both primary infection and reactivation of latent virus transported transsynaptically, anterogradely, and retrogradely. It has also been reported that HSV1 can be reactivated in the brain, which, according to our in cilico and experimental data, might be triggered by body burden dioxin via the AhR-Arnt transcriptional pathway. The latter pathway was previously overlooked, as traditionally they have considered that HSV might be reactivated during stress, inflammation, or immunosuppression conditions only.
Best wishes,
Ilya
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