HERVs expression in Autism Spectrum Disorders

• Published in: PloS one 2012-11, Vol.7 (11), p.e48831-e48831
• Main Authors: Balestrieri, Emanuela, Arpino, Carla, Matteucci, Claudia, Sorrentino, Roberta, Pica, Francesca, Alessandrelli, Riccardo, Coniglio, Antonella, Curatolo, Paolo, Rezza, Giovanni, Macciardi, Fabio, Garaci, Enrico, Gaudi, Simona, Sinibaldi-Vallebona, Paola
• Format: Article
• Language: English
• Subjects: Autism; Biology; Cell culture; Child; Child Development Disorders, Pervasive - virology; Child, Preschool; Coding; Deoxyribonucleic acid; DNA; Endogenous retroviruses; Endogenous Retroviruses - genetics; Endogenous Retroviruses - metabolism; Environmental factors; Epigenetics; Female; Gene expression; Genetics; Genomes; Genomics; Humans; Leukocytes (mononuclear); Male; Medicine; Multiple sclerosis; Mutation; Neurodevelopmental disorders; Neurology; Neurosciences; Non-coding RNA; Noncoding DNA; Patients; Pediatrics; Peripheral blood mononuclear cells; Polymerase chain reaction; Qualitative analysis; Quantitative analysis; RNA, Viral - genetics; RNA, Viral - metabolism; Samples; Schizophrenia; Somatotropin; Statistical analysis; Statistical methods; Stimulation; Studies; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048831

Autistic Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder, resulting from complex interactions among genetic, genomic and environmental factors. Here we have studied the expression of Human Endogenous Retroviruses (HERVs), non-coding DNA elements with potential regulatory functions, and have tested their possible implication in autism. The presence of retroviral mRNAs from four HERV families (E, H, K and W), widely implicated in complex diseases, was evaluated in peripheral blood mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV-H, HERV-W and HERV-K families in PBMCs at the time of sampling and after stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR. Differences between groups were evaluated using statistical methods. The percentage of HERV-H and HERV-W positive samples was higher among ASD patients compared to HCs, while HERV-K was similarly represented and HERV-E virtually absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W are differentially expressed in the two groups, with HERV-H being more abundantly expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs compared to healthy controls. PMBCs from ASDs also showed an increased potential to up-regulate HERV-H expression upon stimulation in culture, unlike HCs. Furthermore we report a negative correlation between expression levels of HERV-H and age among ASD patients and a statistically significant higher expression in ASD patients with Severe score in Communication and Motor Psychoeducational Profile-3. Specific HERV families have a distinctive expression profile in ASD patients compared to HCs. We propose that HERV-H expression be explored in larger samples of individuals with autism spectrum in order to determine its utility as a novel biological trait of this complex disorder.