Ancient viruses could be drivers of autism, new research suggests

Virus fossils that became part of our genetic code millions of years ago may be responsible for certain subtypes of autism, a new study has found. Experiments in mouse models have revealed a possible role for these endogenous viral elements and suggest that this should be a further avenue of research.

The human genome is littered with sequences derived from viruses that infected our ancient ancestors. Called endogenous retroviruses (ERV), these genetic elements represent approximately 8% of our genome and come from the ancestors of modern retroviruses such as HIV.

Most of the time, ERVs remain inactive, silenced by the body’s sophisticated regulatory mechanisms. There have been tentative claims that these sequences may be involved in some cases of sporadic amyotrophic lateral sclerosis (ALS); there is also evidence to suggest that they may play a protective role during embryonic development. Overall, however, they remain largely mysterious relics of our genetic history.

A new study, conducted by an international team led by researchers from Kobe University in Japan, has discovered a possible role for VREs in the development of autism.

The experiments were performed using a mouse model of idiopathic autism, that is, autism without a known genetic or environmental cause. Brain scans of two different but related strains of mice, called BTBR/J and BTBR/R, revealed structural differences in 33 brain regions. Most striking was in the corpus callosum, the bundle of nerves that connects the two hemispheres of the brain together.

Further investigations revealed that BTBR/R mice had significantly higher levels of VREs compared to non-autistic mice, and genetic analysis suggested that these VREs had been activated. The authors suggest this is due to a breakdown in the mechanisms that typically keep VREs sitting quietly in the genome, and found that activation leads to an increase in copy number variants (CNVs) – repeated genetic sequences whose number varies from individual to individual – in autistic mice. The study concluded that activating the VRE during fetal development could increase the likelihood of autism.

The team also performed extensive behavioral tests on their two different groups of autistic mice. BTBR/R mice displayed less anxiety than BTBR/J mice. They also performed almost as well as neurotypical mice in a maze test (similar to the one in the video below), showing that they have an almost typical level of spatial learning ability. However, the BTBR/R mice also showed more repetitive behaviors and less willingness to interact socially with other mice, which the researchers call the “core symptoms” of autism.

Links between the corpus callosum and autism have already been established. However, what the researchers found intriguing here was that the BTBR/R mice – which had more classic autistic behavioral traits – actually had a typical corpus callosum, according to their brain scans.

Therefore, even though these two strains of mice have a common ancestry, they show distinct differences in brain structure and behavior.

The authors suggest that BTBR/R, which is the least used mouse model, is actually a more accurate representation of idiopathic autism, and therefore could be important for future study.

They also point to the need for further research into how VRE activation might predispose individuals to the development of autism, particularly in light of previous research that has found distinctive human VRE signatures in people. autistic. It is hoped that in the future, scientists will be able to build a better classification system for the different types of autism.

“Taken together with the demonstrated roles of VRE in CNV formation, our observation of the two BTBR strains provides a living model to describe how the genome evolves into [autism] susceptibility,” the study concludes.

The study is published in Molecular Psychiatry.

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