HERVs Expression in Autism Spectrum Disorders.
Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”, Rome, Italy.
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.
What are HERV – http://en.wikipedia.org/wiki/Endogenous_retrovirus
Endogenous retroviruses (ERVs) are sequences in the genome that are derived from ancient viral infections of germ cells in mammals and other vertebrates; as such their proviruses are passed on to the next generation and now remain in the genome.
Endogenous retroviruses are a variant of a retrovirus which became permanently integrated with its host and is inherited from generation to generation as part of the genome of the host.
Retroviruses are single-stranded RNA viruses that reverse-transcribe their RNA into DNA for integration into the host’s genome. Most retroviruses (such as HIV-1) infect somatic cells, but in very rare cases, it is thought that exogenous retroviruses have infected germline cells (cells that make eggs and sperm) allowing integrated retroviral genetic sequences to be passed on to subsequent progeny, thereby becoming ‘endogenous’. Endogenous retroviruses have persisted in the genome of their hosts for thousands of years. However, they are generally only infectious for a short time after integration as they acquire many inactivating mutations during host DNA replication. They can also be partially excised from the genome by a process known as recombinational deletion. They are thought to play a key role in evolution. Some human ERVs have been implicated in ALS, certain autoimmune diseases, and cancers.