Role of Human Endogenous Retrovirus type K (HERV-K) in immunosenescence : RNA-seq based transcriptomic analysis
Hamal Mishra, Binisha (2018)
2018
Master's Degree Programme in Public and Global Health
Yhteiskuntatieteiden tiedekunta - Faculty of Social Sciences
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Hyväksymispäivämäärä
2018-12-12
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201901021010
https://urn.fi/URN:NBN:fi:uta-201901021010
Tiivistelmä
Background: Immunosenescence, ageing related decline in immunity, leads to increased incident and severity of various infections, reactivation of latent viruses and decline in vaccine responses among the elderly. As the proportion of older population is rising sharply across the globe, fundamental understanding of immunosenescence is vital for prevention, control and treatment of ageing-related diseases among the vulnerable population. Cytomegalovirus (CMV) plays a substantial role in acceleration of immunosenescence. Interestingly, HERV-K (HML-2), the youngest group of human endogenous retroviruses, has been shown to be co-expressed with CMV in several diseases and cancers. Thus, it is rational to hypothesize that HERV-K (HML-2) potentially plays role in immunosenescence.
Subjects and methods: We investigated potential role of HERV-K (HML-2) in immunosenescence using whole genome RNA-sequencing technique with seven young subjects, age=26-32 years and seven older subjects from Vitality 90+ study cohort, age=90+ years. Gene set enrichment analysis (GSEA) was used to elucidate young and older group specific profile of gene ontology (GO) based biological processes. Direction (up or down) of regulation of the significant biological processes among older subjects was investigated with differential gene expression and subsequent over-representation analysis. Genes that were highly correlated (correlation > 0.80 or < -0.80) with HERV-K expression were used for over-representation analysis with GO based biological processes.
Results and Conclusion: Gene set enrichment analysis of nonagenarian and young groups identified significantly large number of biological processes enriched in nonagenarian as compared to young subjects. Differential gene expression analysis identified 347 genes highly correlated with the youngest provirus, 1q22 that were also differentially expressed between the nonagenarian and young groups. Over-representation of those genes uncovered several immunity related genes and biological processes associated with provirus 1q22 among older subjects. Therefore, our results indicate that provirus 1q22 could be a potential player in immunosenescence. Further research with larger datasets with gender variation is needed for deeper understanding.
Subjects and methods: We investigated potential role of HERV-K (HML-2) in immunosenescence using whole genome RNA-sequencing technique with seven young subjects, age=26-32 years and seven older subjects from Vitality 90+ study cohort, age=90+ years. Gene set enrichment analysis (GSEA) was used to elucidate young and older group specific profile of gene ontology (GO) based biological processes. Direction (up or down) of regulation of the significant biological processes among older subjects was investigated with differential gene expression and subsequent over-representation analysis. Genes that were highly correlated (correlation > 0.80 or < -0.80) with HERV-K expression were used for over-representation analysis with GO based biological processes.
Results and Conclusion: Gene set enrichment analysis of nonagenarian and young groups identified significantly large number of biological processes enriched in nonagenarian as compared to young subjects. Differential gene expression analysis identified 347 genes highly correlated with the youngest provirus, 1q22 that were also differentially expressed between the nonagenarian and young groups. Over-representation of those genes uncovered several immunity related genes and biological processes associated with provirus 1q22 among older subjects. Therefore, our results indicate that provirus 1q22 could be a potential player in immunosenescence. Further research with larger datasets with gender variation is needed for deeper understanding.