Transcriptomic analysis of human cytomegalovirus to survey the indirect effects on renal transplant recipients
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Published on: January 31, 2020
Najmeh Parhizgari1, Mohadeseh Zarei Ghobadi2, Farhad Rezaei1
1Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
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.
Insights
Post-transplant human cytomegalovirus (HCMV) infection activates specific biological pathways linked to adverse indirect effects in renal transplant patients. This study identifies key pathways and genes involved in these complications.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- Post-transplant human cytomegalovirus (HCMV) viremia is associated with adverse indirect effects in transplant recipients.
- HCMV-induced immunomodulatory mechanisms are implicated in these indirect effects.
Purpose of the Study:
- To investigate the pathobiological pathways underlying the long-term indirect effects of HCMV in renal transplant (RT) patients.
- To identify specific biological pathways activated by HCMV infection.
Main Methods:
- Whole transcriptome RNA-Seq analysis of peripheral blood mononuclear cells (PBMCs) from RT patients with and without active HCMV infection.
- Identification of Differentially Expressed Genes (DEGs) and subsequent Gene Ontology (GO) and pathway enrichment analyses.
- Validation of key gene expressions using RT-qPCR in a larger cohort of RT patients.
Main Results:
- Identification of 140 up-regulated and 100 down-regulated DEGs in HCMV-infected RT patients.
- Enrichment of DEGs in pathways including IL-18 signaling, AGE-RAGE signaling, GPCR signaling, platelet activation, estrogen signaling, and Wnt signaling.
- Validation of six significant genes (F3, PTX3, ADRA2B, GNG11, GP9, HBEGF) consistent with RNA-Seq findings.
Conclusions:
- This study elucidates specific pathobiological pathways activated during active HCMV infection.
- These identified pathways are potentially linked to the adverse indirect effects observed in transplant patients following HCMV infection.
