HSV, Axonal Transport and Alzheimer‘s Disease: in Vitro and in Vivo Evidence for Causal Relationships

Abstract

HSV, a neurotropic virus, travels within neuronal processes by fast axonal transport. During neuronal infection HSV travels retrograde from the sensory nerve terminus to the neuronal cell body, where it replicates or enters latency. During replication HSV travels anterograde from the cell body to the nerve terminus. Postmortem studies find a high frequency of HSV DNA in the trigeminal ganglia as well as the brain. Studies correlating HSV with Alzheimer‘s disease (AD) have been controversial. Here we review clinical evidence supporting such a link. Furthermore, the author describes experimental data showing physical interactions between nascent HSV particles and host transport machinery implicated in AD. The author concludes that the complexity of this relationship has been insufficiently explored, although the relative ease and nontoxicity of a potential anti-HSV treatment for AD demands further study.

Keywords:

• Aβ
• Alzheimer‘s disease
• amyloid precursor protein
• APP
• cerebrospinal fluid
• CNS
• encephalitis
• fast axonal transport
• HSV
• senile plaques
• trigeminal ganglion
• trigeminal nucleus

Acknowledgements

The author is grateful to RD O‘Connor for discussion and editing of this review, and to present and former laboratory members including: K Kilpatrick, A Gonzales, GJ Ziomek, P Ferland, S Cheng, K MacLaughlin, A Rasin and A Novikov, as well as to the collaborator, P Webster of House Ear Institute, for their comments and questions over the years. The author also thanks the NIH for funding this research into cytoskeletal dynamics, the pathogenic role of transport defects, and HSV as a tool and a pathogen in neurodegenerative diseases.

Financial & competing interests disclosure

Research supported in the author‘s laboratory was supported by NIGMS P5OGM08273, GM47368; NINDS NS046810 and NS062184. The author is an endowed Professor with funds from the Harvey Family Endowment that supported RD O‘Connor and K MacLaughlin in part. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Research supported in the author‘s laboratory was supported by NIGMS P5OGM08273, GM47368; NINDS NS046810 and NS062184. The author is an endowed Professor with funds from the Harvey Family Endowment that supported RD O‘Connor and K MacLaughlin in part. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.