"Post-transplant human cytomegalovirus (HCMV) viremia has been linked to adverse "indirect effects" among transplant patients. HCMV-created immunomodulatory mechanisms could be associated with the indirect effects.
Objective: In the present study, the RNA-Seq whole transcriptome of renal transplant (RT) patients was analyzed to seek the underlying pathobiologic pathways associated with the long-term indirect effects of HCMV.
Methods: To investigate the activated biological pathways in HCMV infection, total RNA was extracted from PBMCs of 2 RT patients with active HCMV and 2 RT patients without infection and then were sequenced using RNA-Seq. The resulted raw data were analyzed by conventional RNA-Seq software to determine the Differentially Expressed Genes (DEGs). Afterward, Gene Ontology (GO) and pathway enrichment analyses were conducted to determine the enriched pathways and biological processes by DEGs. Eventually, the relative expressions of some significant genes were validated in the twenty external RT patients.
Result: The analysis of RNA-Seq data related to RT patients with HCMV active viremia led to the identification of 140 up-regulated and 100 down-regulated DEGs. KEGG pathway analysis revealed the enrichment of DEGs in IL18 signaling, AGE-RAGE signaling pathway in diabetic complications, signaling by GPCR, Platelet activation, signaling and aggregation, Estrogen signaling pathway and signaling by Wnt due to HCMV infection. The expression levels of six genes involved in enriched pathways including F3, PTX3, ADRA2B, GNG11, GP9, HBEGF were then verified using RT-qPCR. The results were in consistent with RNA-Seq resultsoutcomes.
Conclusion: This study specifies some pathobiological pathways which are activated in HCMV active infection and could be linked to the adverse indirect effects caused by HCMV infection in transplant patients."