Double-stranded RNA and reverse transcriptase signatures of endogenous retroviruses after exposure to spaceflight environment related stressors.

Spaceflight is known to alter immune function and has been associated with reactivation of latent viruses, such as herpesviruses, in astronauts. The human and rodent genomes also contain thousands of endogenous retroviral sequences (ERVs) which are remnants of ancient germline retroviral infections that have been epigenetically silenced over evolutionary time. Although transcriptionally repressed under baseline conditions, ERV-associated molecular signatures such as double-stranded RNA and reverse transcriptase activity can re-emerge in response to environmental stress. Expression of these has been implicated in a wide range of human disorders, including neurological, autoimmune, and carcinogenic conditions. As exploration missions extend into deep space, astronauts will be chronically exposed to a unique combination of stressors, including microgravity and high-energy ionizing radiation, raising the question of whether these exposures could perturb ERV regulation. In this pilot study, we investigated ERV-associated surrogate markers in both cell and rodent models following simulated spaceflight stressors. We observed early induction of ERV-linked molecular signatures shortly after exposure, as well as persistent evidence of these signatures that remained detectable over a year after space radiation challenge in vivo. Together these findings indicate that spaceflight related stressors can elicit both acute and long-lasting epigenetic perturbations leading to transcriptional activation of ERV-related genetic loci. Given the cumulative and repeated exposure to both space radiation and microgravity that astronauts will experience during long duration missions, these results highlight the need for deeper investigation into ERV biology in the space environment and its potential implications for astronaut health.