Ancient virus infection is linked with addiction

Many regions in the human genome are composed of “junk DNA” that do not code for proteins in the cell. 

While these DNA codes are generally viewed as redundant and seemingly serve no particular function in the human body, some codes could be evidence of evolutionary scars left behind from ancient viral infections from the time of our primate ancestors.

Human endogenous retroviruses (HERVs) are the remnants of ancient viral infections in our DNA from infections in germline cells, which are involved in reproduction. Passed down from generation to generation, these retroviral genes can become inactivated as a result of inactivating mutations.

It is known that approximately four to eight percent of the human genome is composed of HERVs. Although most of the HERVs ceased to proliferate millions of years ago, the remaining HERV-K HML-2 (HK2) retrovirus may still be active.

How these ancient viral infections, sometimes called fossil viruses, affect the human body and behavior is unclear. 

A recent study lead by Gkikas Magiorkinis of the University of Athens and Aris Katzourakis of the University of Oxford sheds light on this question by examining a HIV-positive population in Greece and a population with chronic hepatitis C virus (HCV) infection in the United Kingdom.

Magiorkinis works at the Department of Hygiene, Epidemiology and Medical Statistics. Katzourakis is a professor of Evolution and Genomics, with a research focus on studying the long-term evolutionary biology of viruses. Their recent results were published in the Proceedings of the National Academy of Sciences.

The research demonstrated that HK2 is found close to RASGRF2,­ a gene involved in dopaminergic activity in the brain, more frequently in drug addicts, thereby indicating an association with addiction. 

Dopamine is an important neurotransmitter involved in the human reward pathway, so the proximity of HK2 to RASGRF2 may cause harmful interactions and lead to addiction.

Magiorkinis expressed the excitement for HERVs’ potential in human pathology and stated that their research evidence serves as a strong proof for their hypothesis.

“Most people think these ancient viruses are harmless. From time to time, people have shown overexpression of HK2 in cancer, but it has been difficult to distinguish cause from effect,” Magiorkinis said, according to ScienceDaily. “Back in 2012, following a 20-year controversy regarding their pathogenic roles in humans, we sought to test the high-risk hypothesis that HERVs can be responsible for human disease.”

The team’s proposal was supported by the Medical Research Council (MRC), and now the team has gathered strong proof that HERVs can be pathogenic. 

“For the first time, we are able to make a distinction between cause and effect in HERV pathogenicity,” Magiorkinis said. 

In one part of the experiment, the research team looked the for the presence of HK2 in the RASGRF2 gene of HIV-positive patients. 

They compared their results between 102 people infected with HIV from drug use and 100 people infected by other transmission routes. 

The results revealed that HK2 was twice as likely to be found in people who injected drugs (PWIDs), suggesting the ancient virus’ role in addictive behavior.

The researchers then studied patients in Britain with HCV infection. The results supported the previous results and found that HK2 was 3.5 times more frequent in PWIDs compared to other patients infected through other means.

Katzourakis emphasized the novelty of their research results in the understanding of HERV’s and HK2’s effect on human behavior.

“We know of clear biological roles for a small number of human endogenous retroviruses. 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,” Katzourakis said, according to ScienceDaily. “Our study shows for the first time that rare variants of HK2 can affect a complex human trait.”

While the results and observations made in this study do not absolutely confirm HK2’s role in addiction, it does demonstrate how our evolutionary history can still affect us to the present day. 

“I believe that a significant part of this unexplained disease diversity will be understood by studying this difficult-to-understand ‘dark’ genome,” Magiorkinis said, according to CNN.