Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders

Pathog Dis. 2013 Dec;69(3):240-61. doi: 10.1111/2049-632X.12077. Epub 2013 Sep 2.

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.

Keywords: Alzheimer's disease; mood disorders; multiple sclerosis; schizophrenia.

MeSH terms

  • Autoimmunity
  • Computational Biology
  • Evolution, Molecular
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Genome-Wide Association Study
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism
  • Herpesvirus 1, Human / physiology*
  • Host-Pathogen Interactions* / genetics
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Mental Disorders / genetics*
  • Mental Disorders / metabolism
  • Models, Biological
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / metabolism
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Selection, Genetic
  • Signal Transduction

Substances

  • Receptors, Virus