*Purpose: Cytomegalovirus (CMV) viremia and disease continues to cause significant morbidity and mortality in kidney transplant patients with clinical complications including organ rejection and death. Gene expression dynamics in viremic patients from time of transplant to time of viremia and post-viremia has not been well studied to-date. We proposed to assess gene expression early and late after start of CMV viremia to determine the acute and chronic changes in immune cells. Here we present RNA-seq data from 29 viremic patients at 4 timepoints (baseline, 1 week post-viremia, 1 month post-viremia, and 9-18 months post-transplant).

*Methods: Kidney transplant recipients at risk for CMV disease who developed CMV viremia were identified from an ongoing IRB-approved study. RNA-seq was performed on RBC-lysed whole blood samples that had been stored in RNAlater at baseline, 1 week post-viremia, 1 month post-viremia, and 9-18 months post-viremia start. The raw reads were processed using a standard RNA-seq pre-processing pipeline. Differential expression analysis was performed using the R package, edgeR. Pathway analysis was performed using Ingenuity Pathway Analysis. Time-course analysis of pathways was performed using the R package, TcGSA.

*Results: Pairwise differential expression analysis between timepoints in the viremic patients revealed that the greatest amount of transcriptomic change occurred between baseline and 1 week post-viremia timepoints (845 genes down-regulated, 877 genes up-regulated, adjusted p ≤ 0.05). Time-course gene set analysis of the significantly enriched pathways that revealed that 15 of 18 pathway gene sets had a significant time-trend. Although some of the gene sets that were significantly down- or up-regulated at 1 week returned to baseline levels at the 9-18 month timepoint, some of the pathways such as “Cytotoxic T Lymphocyte-mediated Apoptosis of Target Cells”, “Interferon Signaling” and “CCR5 Signaling in Macrophages” remained up-regulated at the 9-18 month timepoint.

*Conclusions: Differential expression analysis, pathway analysis, and time-course gene set analysis, revealed the dynamics of significantly enriched genes and pathways involved in innate and adaptive immune response to CMV viremia in kidney transplant patients. Although early changes 1 week after viremia were most striking, we also demonstrated a significant subset of gene sets that are up-regulated immediately after CMV viremia but do not totally revert to baseline levels, even 9-18 months post-transplant. These findings provide a mechanistic framework to identify biomarkers for risk assessment, guiding therapy and measuring vaccine efficacy.

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