Direct evidence of alteration to the human neural intracellular trafficking system following exposure to HSV: A systematic review

AbstractThere is a growing interest in the potential role that lifelong chronic viral infections may play in the aetiology of certain neurodegenerative diseases. For example, the disruption of neuronal intracellular trafficking by repeated reactivations of latent herpes viruses has been proposed as a possible inductive agent of Alzheimers disease (AD). This systematic review examines the extent of primary data that have examined the effect(s) of herpes viruses on the human intraneuronal trafficking (HINT) system. Three databases (MEDLINE, SCOPUS, and Web of Science), were repeatedly searched. 5782 articles were identified, of which 13 met our eligibility criteria, and five were included for qualitative synthesis. Four of the five collated studies presented data from cell culture experiments, wherein herpes simplex virus 1 (HSV-1) altered lysosomal load, lysosomal function, and activity-regulated cytoskeleton-associated protein (ARC) mRNA/protein expression in a cell-type/species specific manner. One of the five studies was a clinical case study that presented observations on a fatal herpes encephalopathy, wherein the neuronal endoplasmic reticulum and Golgi apparatus were ablated by the rampant infection. Unfortunately, there is an extremely limited amount of primary research examining the effects of herpes viruses on the HINT system, but within that limited pool there is clear evidence of cell type-/stage- specific responses to infection. Future studies investigating herpes infection in neurodegenerative disease need to utilise cell-type and species- specific models if they are to have any hope of extrapolating to a clinical setting.