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Herpes simplex (HSV-1) can promote beta-amyloid deposition and tau phosphorylation, demyelination or cognitive deficits relevant to Alzheimer’s disease or multiple sclerosis and to many neuropsychiatric disorders with which it has been implicated. A seroprevalence much higher than disease incidence has called into question any primary causal role. However, as also the case with risk promoting polymorphisms, (also present in control populations) any causal effects are likely to be conditional. During its life cycle, the virus binds to many proteins and modifies the expression of multiple genes creating a host/pathogen interactome involving 1347 host genes. This dataset is heavily enriched in the susceptibility genes for multiple sclerosis (P= 1.3E-99) >Alzheimer’s disease > schizophrenia > Parkinsonism > depression> bipolar disorder> childhood obesity> chronic fatigue> autism > and anorexia (P=0.047) but not ADHD, a relationship maintained for GWAS datasets in multiple sclerosis and Alzheimer’s disease. Overlapping susceptibility gene/interactome datasets disrupt signalling networks relevant to each disease, suggesting that disease susceptibility genes may filter the attentions of the pathogen towards particular pathways and pathologies. In this way, the same pathogen could contribute to multiple diseases in a gene-dependent manner and condition the risk promoting effects of the genes whose function it disrupts. This article is protected by copyright. All rights reserved.