Effect of aging on the transcriptomic changes associated with the expression of the HERV-K (HML-2) provirus at 1q22.

BACKGROUND: The human genome contains remnants of ancient retroviral infections called human endogenous retroviruses (HERV). Their expression is often observed in several diseases of autoimmune or inflammatory nature. However, the exact biological mechanisms induced by HERVs are still poorly understood. We have previously shown that several HERVs of the HERV-K (HML-2) family are strongly transcribed in the peripheral blood mononuclear cells (PBMC) derived from young and old individuals. To examine the potential functional consequences of HERV-K (HML-2) expression, we have now analyzed the correlation of its expression with age-associated changes in the transcriptome using gene set enrichment analysis (GSEA). We focused our analysis on the HERV-K (HML-2) provirus at 1q22, also known as ERVK-7. RESULTS: The genes strongly correlating with the expression of HERV-K (HML-2) provirus at 1q22 expression were found to be almost entirely different in young and old individuals. The number of genes strongly correlating (Pearson correlation coefficient ≥ 0.7) with 1q22 expression was 946 genes in the old and 435 in the young, of which only 41 genes correlated strongly in both. Consequently, the related gene ontology (GO) biological processes were different. In the older individuals, many of the highest correlating processes relate to the function of neutrophils. CONCLUSIONS: The results of this work suggest that the biological processes associated with the expression of HERV-K (HML-2) provirus at 1q22 are different in the blood of young and old individuals. Specifically, a strong association was found in the older individuals between neutrophil activity and the expression of the HERV-K (HML-2) provirus at 1q22. These findings offer insight into potential effects of altered HERV expression in older individuals.