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P-1522. Transcriptional Cascade in Cytomegalovirus Infection
Abstract   Open access   Peer reviewed

P-1522. Transcriptional Cascade in Cytomegalovirus Infection

Arya Zandvakili, Ming Li, Qiaolin Hu, Mrutyunjaya Parida and Jeffery Meier
Open forum infectious diseases, Vol.13(Supplement_1)
01/11/2026
DOI: 10.1093/ofid/ofaf695.1706
PMCID: PMC12792612
url
https://doi.org/10.1093/ofid/ofaf695.1706View
Published (Version of record) Open Access

Abstract

Background During lytic infection, cytomegalovirus (CMV), like other Herpesviruses, follows a cascade of gene expression that is classically modeled by categorizing genes as Immediate Early (IE, involved in triggering Early gene expression), Early (E, involved in viral DNA replication), and Late (L, involved in virion assembly). Historically, this cascade is characterized by measuring levels of mRNA and protein products of viral genes. However, mRNA and protein levels are a function of multiple different processes. Without isolating a specific step in gene expression, identifying mechanisms that coordinate the expression of IE, E, and L genes is challenging. Here we aim to characterize the cascade of gene expression specifically at the level of transcription, the process by which DNA is expressed as RNA. By isolating transcriptional activity, we may be able to better identify the mechanisms that coordinate expression, which may serve as therapeutic targets. Methods We conducted a novel analysis of a previously published Precision Run-On Sequencing (PRO-seq) dataset. PRO-seq allows for genome-wide measurement of transcriptional activity at single-nucleotide resolution. This dataset was produced by infecting cultured human foreskin fibroblasts (HFFs) with CMV and performing PRO-seq at 4-, 12-, 24-, 48-, and 72-hours post-infection (covering the entire CMV life cycle). Results Hierarchical clustering was used to cluster both coding and non-coding genes into groups with similar temporal patterns of transcription. Some groups of genes are transcriptionally active at defined time-periods, consistent with the classic cascade model. Additionally, we find evidence of genes with transcriptional activity inconsistent with the classic cascade model – specifically, genes with transcriptional activity persistent throughout viral life cycle and genes with intermittent transcriptional activity. Conclusion Preliminary analysis of CMV transcription activity suggests coordinated transcription as well as inconsistencies with the classic cascade model of Herpesvirus gene expression. Next steps include: (1) test results through separate assays of transcriptional activity; (2) identify mechanisms of coordinated transcription; and (3) assess cell-type differences. Disclosures All Authors: No reported disclosures
 Gene Expression Cytomegalovirus Infections

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