Abstract
BackgroundThe 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.ResultsThe 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.ConclusionsThe 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.
Highlights
The human genome contains remnants of ancient retroviral infections called human endogenous retroviruses (HERV)
The old individuals had 4 of the top 20 most significantly enriched gene ontology (GO) terms involve neutrophils (Table 1), which according to the hypergeometric test results in a very low p-value of 4.96e-13, indicating significance (p-value < 0.05)
The results of this work suggest that the biological processes associated with the expression of HERV-K (HML2) provirus at 1q22 are different in the blood of young and old individuals
Summary
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. An estimated 8% of the human genome consists of endogenous retroviruses, which are remnants of exogenous retroviral infections that have integrated into the human germline throughout millions of years. The majority of these human endogenous retrovirus (HERV) proviruses. In our previous work [16], we found the HERV-K (HML-2) at 1q22 to be significantly higher expressed (p-value < 0.05) in nonagenarian PBMCs (Peripheral Blood Mononuclear Cells) compared to young controls (Fig. 1), while expression of 1q23.3 was found to be very low. The provirus at 1q22 is known as K102 and ERVK-7 [21]
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