Human Endogenous Retroviruses Type W (HERV-W): an Epiphenomenon or the Missing Link in Schizophrenia?

07/13/2017

Hyun Min (Liz) Geum​

Volume 2
Fall 2016 / Winter 2017

Human endogenous retroviruses (HERVs) are remnants of ancient infection events that resulted in an integration of provirus genomes into germline DNA; these retroviral sequences account for about 8% of the human genome. One biologically active family of HERVs, HERV-W, has been implicated in the pathogenesis of several autoimmune and psychiatric disorders, including schizophrenia (SZ). SZ is a severe and chronic multifactorial disorder, ranking as one of the leading causes of disability worldwide. Various infectious agents, including herpes and influenza, have long been suspected to be involved in the etiology of SZ. However, the exact mechanism by which infectious agents are involved is unclear. Because it has been established that such infectious agents can activate HERV-W elements, including the envelope protein, which can induce neurotoxicity and thereby lead to symptomatic onset of SZ, HERV-W has been suggested as the missing link between infectious events and SZ pathogeny. This article provides an overview of the HERV biology and its biological significance, the evidence supporting the association between HERV-W and SZ, and the proposed molecular and immunological mechanisms involving HERV-W and infectious events leading to SZ pathogenesis. Understanding the biology of HERV-W and its interaction with the environment in SZ may help us better elucidate the pathophysiology of many debilitating multifactorial neurological diseases whose etiopathogeneses remain elusive, and inform us about novel diagnostic and therapeutic strategies.