Aberrant Expression of Human Endogenous Retroviruses and SETDB1 in Adolescents with Anorexia Nervosa

Human endogenous retroviruses (HERVs) represent 8% of our genome. They are remnants of ancient infections of germinal cells. HERVs are no longer infectious, but their enhanced expression is implicated in several diseases, including neuropsychiatric disorders. Their transcription is regulated by TRIM28 and SETDB1, which are involved in the regulation of epigenetic processes, in neural cell differentiation, and brain inflammation. We explored the expressions of HERVs and TRIM28/SETDB1 in adolescents affected by anorexia nervosa (AN). Through real-time PCR, we assessed the transcription levels of pol genes of HERV-H, -K, and -W, of env genes of Syncytin 1 (SYN1), Syncytin 2 (SYN2), and of HERV-W, and of TRIM28 and SETDB1 in whole blood of 37 adolescents with AN and in healthy controls (HCs) of comparable age. HERV-H-pol, HERV-K-pol and SETDB1 transcriptional levels were significantly higher in adolescents with AN as compared with HCs, while HERV-W-pol and -env were downregulated in the former. No differences were observed for SYN1, SYN2, and TRIM28 between the two groups. The observed expression pattern of HERVs is specific for AN as compared to other neuropsychiatric disorders. These aberrant expressions suggest a potential role of retroviral elements in the pathophysiology of AN, opening the way for innovative diagnostic and therapeutic strategies.