Human endogenous retrovirus type W (HERV-W) in schizophrenia: A new avenue of research at the gene–environment interface

Abstract

Objectives. Provide a synthetic review of recent studies evidencing an association between human endogenous retrovirus-W (HERV-W) and schizophrenia. Methods. Bibliography analysis and contextual synthesis. Results. Epidemiological studies suggest that the aetiology of schizophrenia is complex and involves a complex interplay of genetic and environmental factors such as infections. Eight percentof the human genome consists of human endogenous retroviruses (HERV), and this part of the genome was previously thought to be without importance, but new research has refuted this. HERVs share similarities with viruses and it is assumed that HERVs are present in the genome as a result of retroviruses infecting germ line cells many million years ago. A specific type of HERVs, called HERV-W, has through several recent studies been associated with schizophrenia. Elevated transcription of HERV-W elements has been documented, and antigens of HERV-W envelope and capsid proteins have been found in blood samples from patients. Viruses that have been implicated in pathology of schizophrenia, such as herpes and influenza, have been shown to activate HERV-W elements, and such activation has been associated with elevated biomarkers of systemic inflammation. New research indicates that HERV-W may be an important genetic factor interplaying with the environmental risk factor of infections and that, through this, HERV-W may be important for disease pathogenesis. Conclusions. A lifelong scenario of a detrimental interaction between infectious agents and HERV-W genes may decipher the actual development and course of schizophrenia. Further research is needed to find out if specific treatment strategies could reduce the expression of HERV-W and if this will be associated with remission.

Key words::

• Schizophrenia
• neuroinflammation
• genetics
• endogenous retrovirus
• HERV-W

Acknowledgments

The authors are supported by the “Institut National de la Santé et de la Recherche Médicale” (INSERM), the “Agence Nationale pour la Recherche” (ANR; NEURO 2009, V.I.P. project), the fondation FondaMental (Fondation de Coopération Scientifique pour le développement de la recherche et des soins en santé mentale), and GeNeuro Innovation, France.

Statement of Interest

Hervé Perron and Raphaël Faucard are financially supported by GeNeuro/GeNeuro Innovation. All other authors declare that they have no conflicts of interest.