Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model
Karamitros T., Hurst T., Marchi E., Karamichali E., Georgopoulou U., Mentis A., Riepsaame J., Lin A., Paraskevis D., Hatzakis A., McLauchlan J., Katzourakis A., Magiorkinis G.
Significance The human genome is “littered” with remnants of ancient retrovirus infections that invaded the germ line of our ancestors. Only one of these may still be proliferating, named HERV-K HML-2 (HK2). Not all humans have the same HK2 viruses in their genomes. Here we show that one specific uncommon HK2, which lies close to a gene involved in dopaminergic activity in the brain, is more frequently found in drug addicts and thus is significantly associated with addiction. We experimentally show that HK2 can manipulate nearby genes. Our study provides strong evidence that uncommon HK2 can be responsible for unappreciated pathogenic burden, and thus underlines the health importance of exploring the phenotypic roles of young, insertionally polymorphic HK2 integrations in human populations.