Interplay between activation of endogenous retroviruses and inflammation as common pathogenic mechanism in neurological and psychiatric disorders

Human endogenous retroviruses (ERVs) are ancestorial retroviral elements that were integrated into our genome through germline infections and insertions during evolution. They have repeatedly been implicated in the aetiology and pathophysiology of numerous human disorders, particularly in those that affect the central nervous system. In addition to the known association of ERVs with multiple sclerosis and amyotrophic lateral sclerosis, a growing number of studies links the induction and expression of these retroviral elements with the onset and severity of neurodevelopmental and psychiatric disorders. Although these disorders differ in terms of overall disease pathology and causalities, a certain degree of (subclinical) chronic inflammation can be identified in all of them. Based on these commonalities, we discuss the bidirectional relationship between ERV expression and inflammation and highlight that numerous entry points to this reciprocal sequence of events exist, including initial infections with ERV-activating pathogens, exposure to non-infectious inflammatory stimuli, and conditions in which epigenetic silencing of ERV elements is disrupted.

Automated summary

Human endogenous retroviruses (ERVs) are retroviral elements integrated into our genome through germline infections and insertions, and have been implicated in the pathophysiology of various disorders, particularly those affecting the central nervous system. Increasing evidence suggests that the induction and expression of ERVs are associated with neurodevelopmental and psychiatric disorders, and a common factor in these disorders is the presence of chronic inflammation. This review discusses the bidirectional relationship between ERV expression and inflammation, and identifies several pathways that contribute to this relationship.