title: Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.
abstract: Herpes simplex virus 1 (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 data set 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 attention deficit hyperactivity disorder, a relationship maintained for genome-wide association study data sets in multiple sclerosis and Alzheimer's disease. Overlapping susceptibility gene/interactome data sets 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.
authors.affiliation: PolygenicPathways, Hastings, East Sussex, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Carter
mesh_terms: D015551:Autoimmunity; D019295:Computational Biology; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D009422:Nervous System Diseases / Q000235:genetics* / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D015398:Signal Transduction
chemical_list: D011991:Receptors, Virus
keywords: Alzheimer's disease; mood disorders; multiple sclerosis; schizophrenia