Human endogenous retroviruses and the nervous system

Within the human genome reside thousands of retrovirus-like sequences which comprise nearly 8% of the human genome. Originating from ancient retroviruses that overcame host defense mechanisms and permanently integrated into the genomes of our early and more recent primate and hominid ancestors, these provirus remnants are referred to as human endogenous retroviruses (HERVs). HERV is a broad heading for numerous families of retroviruses which were able to infect germline cells over the course of human evolution. Subsequent to integration in the genome, transmission of HERVs occurred in a Mendelian fashion, overriding the need to spread by exogenously acquired infection; however, it is clear that epigenetic and antiviral responses were essential in silencing the expression of these integrated proviruses over time. Yet, current research indicates that not all HERVs remain silent passengers, as reactivation of HERVs is associated with neurologic disorders - although they have not been shown to be causative of any human disease. This chapter focuses on the past and present activity of HERVs in humans, known triggers of HERV expression in the central nervous system, as well as putative pathologic consequences of endogenous retroviruses in the inception and exacerbation of neurologic disease.