Human Cytomegalovirus Infection Elicits Global Changes in Host Transcription by RNA Polymerases I, II, and III

Christopher B Ball; Mrutyunjaya Parida; Ming Li; Benjamin M Spector; Gustavo A Suarez; Jeffery L Meier; David H Price

doi:10.3390/v14040779

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Human Cytomegalovirus Infection Elicits Global Changes in Host Transcription by RNA Polymerases I, II, and III

Journal article

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Human Cytomegalovirus Infection Elicits Global Changes in Host Transcription by RNA Polymerases I, II, and III

Christopher B Ball, Mrutyunjaya Parida, Ming Li, Benjamin M Spector, Gustavo A Suarez, Jeffery L Meier and David H Price

Viruses, Vol.14(4), p.779

04/09/2022

DOI: 10.3390/v14040779

PMCID: PMC9026722

PMID: 35458509

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Abstract

How human cytomegalovirus (HCMV) infection impacts the transcription of the host genome remains incompletely understood. Here, we examine the global consequences of infection of primary human foreskin fibroblasts (HFFs) on transcription by RNA polymerase I, II, and III over the course of a lytic infection using PRO-Seq. The expected rapid induction of innate immune response genes is observed with specific subsets of genes exhibiting dissimilar expression kinetics. We find minimal effects on Pol II initiation, but increased rates of the release of paused Pol II into productive elongation are detected by 24 h postinfection and pronounced at late times postinfection. Pol I transcription increases during infection and we provide evidence for a potential Pol I elongation control mechanism. Pol III transcription of tRNA genes is dramatically altered, with many induced and some repressed. All effects are partially dependent on viral genome replication, suggesting a link to viral mRNA levels and/or a viral early-late or late gene product. Changes in tRNA transcription are connected to distinct alterations in the chromatin state around tRNA genes, which were probed with high-resolution DFF-ChIP. Additionally, evidence is provided that the Pol III PIC stably contacts an upstream -1 nucleosome. Finally, we compared and contrasted our HCMV data with results from published experiments with HSV-1, EBV, KSHV, and MHV68. We report disparate effects on Pol II transcription and potentially similar effects on Pol III transcription.

Cytomegalovirus Infections - genetics

Humans

Promoter Regions, Genetic

RNA Polymerase I - genetics

RNA Polymerase I - metabolism

RNA Polymerase II - genetics

RNA Polymerase II - metabolism

RNA Polymerase III - genetics

RNA Polymerase III - metabolism

RNA, Transfer - genetics

Transcription, Genetic

Details

Title: Subtitle: Human Cytomegalovirus Infection Elicits Global Changes in Host Transcription by RNA Polymerases I, II, and III
Creators: Christopher B Ball - University of Iowa
Mrutyunjaya Parida - University of Iowa
Ming Li - University of Iowa
Benjamin M Spector - University of Iowa
Gustavo A Suarez - University of Iowa
Jeffery L Meier - University of Iowa
David H Price - University of Iowa
Resource Type: Journal article
Publication Details: Viruses, Vol.14(4), p.779
DOI: 10.3390/v14040779
PMID: 35458509
PMCID: PMC9026722
NLM abbreviation: Viruses
ISSN: 1999-4915
eISSN: 1999-4915
Grant note: GM126908 / NIH HHS R35 GM126908 / NIGMS NIH HHS AI130453 / NIH HHS BX004434 / VA AI007533 / NIH HHS
Language: English
Date published: 04/09/2022
Academic Unit: Infectious Diseases; Epidemiology; Pathology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984293074002771

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