Transcriptional Upregulation of HERV-env Genes Under Simulated Microgravity

Human endogenous retroviruses (HERVs) constitute about 8% of the human genome. The overexpression of HERVs has been detected in various inflammatory disorders like neuro-inflammation disorders and cancer. Interestingly, it has been reported that stress conditions facilitate HERV expression. Space travel exposes astronauts to microgravity environments (a stress condition), which may result in the activation of HERVs and might influence pathogenic outcomes during and after space flight. This study aimed to elucidate the transcriptional activity of three HERV families (W, K, and H) and cytokine genes (<i>IL-1</i>, <i>IL-6</i>, and <i>TNF</i>-α) in different cell lines under microgravity (μg) conditions and compare them with the results obtained under normal gravity (ng; 1g). We evaluated the expression of HERVs (HERV-K <i>env</i>, HERV-K <i>gag</i>, HERV-W <i>env</i>, and HERV-H <i>env</i>) and cytokine gene expression (<i>IL-1</i>, <i>IL-6</i>, and <i>TNF</i>-α) in neuroblastoma (SH-SY5Y), HEp-2, and Caco-2 cell lines under simulated μg and 1g conditions. In SH-SY5Y cells, the expression level of the <i>IL-1</i>, <i>IL-6</i>, HERV-H <i>env</i>, HERV-K <i>env</i>, HERV-K <i>gag</i>, and HERV-W <i>env</i> genes was significantly increased when exposed to short-term μg (3 and 6 h). The expression of <i>TNF</i>-α remained unchanged throughout all time points. Additionally, in Caco-2 cells, the expression of the HERV-K <i>env</i>, HERV-K <i>gag</i>, and <i>IL-1</i> genes was significantly higher after 6 h of incubation in μg conditions compared to 1g. There was no statistically significant difference in the expression levels of the HERV-W <i>env</i>, HERV-H <i>env</i>, <i>IL6</i>, and <i>TNF</i>-α genes between the μg and 1g conditions. Moreover, in HEp-2 cells, the expression of the <i>IL-1</i>, <i>IL6</i>, <i>TNF</i>-α, HERV-H <i>env</i>, HERV-K <i>env</i>, HERV-K <i>gag</i>, and HERV-W <i>env</i> genes significantly increased following short-term incubation in μg (3 h, 6 h) and then decreased to levels comparable to those observed in the 1g condition. Taken together, the dysregulation of cytokine and HERV gene expression was observed under the simulated μg condition. The patterns of these dysregulations varied throughout cell lines, which demands further investigation for human health protection in space.