An international team of researchers has revealed that an ancient retrovirus, found in between 5 and 10 percent of the world's population, is significantly associated with addictive behavior. The study uncovered a connection between the retrovirus and a specific gene that could make individuals more prone to a variety of addictive behaviors.
Traces of ancient retrovirus infections can be found all over the human genome. For the most part these tiny alterations in our DNA are thought to not have much pathogenic effect on the human body, but one particular retrovirus, called HK2, came to the attention of researchers. HK2 has been occasionally found integrated into a gene called RASGRF2. This specific gene is known to play a role in the brain's dopaminergic activity, and prior research has revealed links between RASGRF2 and alcohol addiction.
The first part of the new research examined two different cohorts, one in the UK and one in Greece. The Greek cohort was a collection of HIV-positive individuals, half of which were infected through intravenous drug use and the other half through alternative transmission routes. The UK cohort comprised subjects infected with hepatitis C, again split between those infected through intravenous drug use and those infected in other ways.
Across both groups the research found that those subjects with a history of intravenous drug use were between two and three times more likely to have traces of HK2 within the RASGRF2 gene. This offered the scientists a decent indication that HK2 could be altering the expression of a that particular gene to predispose certain individuals to addictive behavior.
The next stage of the study tried to understand whether HK2 was specifically modifying the expression of RASGRF2. To answer this question the researchers used CRISPR technology to insert HK2 into the exact location it had been identified in human DNA within the RASGRF2 gene. According to the researchers, the results confirmed that this insertion did indeed result in significant transcriptional and phenotype changes.
Of course a great deal of this research remains entirely hypothetical, but the study does suggest that HK2 enhances dopaminergic activity via RASGRF2. The subsequent hypothesis is that this increases the potential for addiction in individuals that carry this unique genetic trace.
"We know of clear biological roles for a small number of human endogenous retroviruses," says Timokratis Katzourakis, co-director of the new study. "However, there has never before been strong evidence in support of a role in human biology of an endogenous retrovirus that is unfixed, in other words not shared by all individuals in the population. Our study shows for the first time that rare variants of HK2 can affect a complex human trait."
Further work still needs to be done to better understand this newly revealed mechanism. As well as MRI experiments to examine brain activity in those individuals with the HK2 integrated RASGRF2 gene, the research suggests that this specific trigger is not just associated with drug addiction but can potentially imply a predisposition to more general addictive behavior.
The study was published in the journal Proceedings of the National Academy of Sciences.
Source: University of Oxford
