Analysis of host and viral nascent and steady-state RNA levels in a human neuronal model of herpes simplex virus 1 infection.

Overview

1. Department of Microbiology and Immunology, Cornell University Baker Institute for Animal Health, Ithaca, New York, United States of America
2. Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America

Abstract

We used precision nuclear run-on with sequencing (PRO-seq) in conjunction with quantitative RT-qPCR to map transcription, and transcript abundance in terminally differentiated LUHMES neurons before (mock) and after infection with Herpes Simplex Virus 1 (HSV-1). Initial PRO-seq analysis of cellular transcription demonstrated that the mock-infected differentiated LUHMES neurons expressed genes associated with differentiated neurons. This gene set included transcription of genes related to dopaminergic signaling, cell adhesion, and neuronal cell differentiation. By contrast, epithelial cells transcribed genes involved in cell cycle progression and DNA damage repair. PRO-Seq analysis of HSV-1-infected LUHMES neurons indicated only modest transcription of viral genomes. Additionally, genes of LUHMES neurons maintained RNA polymerase II (Pol II) promoter proximal pausing whereas we previously showed HSV-1 infection decreases promoter-proximal pausing on genes of epithelial cells. PRO-Seq and RT-qPCRanalysis were performed during a time course of infection, spanning both acute and latent phases. The results from the acute infection demonstrated slower rates of transcription, viral mRNA accumulation, and viral genome replication compared to undifferentiated, non-neuronal cells. RT-qPCR indicated that steady-state transcripts from all viral gene kinetic classes increased in abundance from 1 h to 24 h post-infection. This accumulation correlated with an increase in transcription on the same genes as demonstrated by PRO-seq. In contrast, the latent phase of infection was distinguished by high levels of transcription on all viral genes, but very low viral transcript abundance. These results indicate that viral gene transcription initiation does not correlate with viral transcript abundance during the latent phase, and suggest that blocks to RNA polymerase processivity and other components of the RNA life cycle likely contribute to maintenance of latency in LUHMES neurons.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• geo:GSE286720, at NCBI GEO; found in “Data Availability”

Data Availability

The PRO-seq data used in this manuscript is available with the following GEO accession number: GSE286720. The link is https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286720. The .bw files are not found with the sample GSM numbers. To access the .bw files in the GEO omnibus, scroll down past the samples listed with the GSM files, to the table called Supplementary file. This table contains a TAR download extension of the .bw files. You can download it using the http link or create a custom download to the directory of your choice. All viruses used in this study can be provided upon request. The index file used for the sequencing can be found at https://github.com/Baines-Lab/Public/tree/main/HSV-1.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 9 MeSH terms, 1 funder, 149 references.

Cite

This paper

Birkenheuer, C. H., Edwards, T. G., Bloom, D. C., & Baines, J. D. (2026). Analysis of host and viral nascent and steady-state RNA levels in a human neuronal model of herpes simplex virus 1 infection. PLoS pathogens, 22(9), e1014603. https://doi.org/10.1371/journal.ppat.1014603

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s44400-026-00066-y [code]

A high-throughput, quantitative platform using 2D dissociated human cerebral organoids to model neuroinflammation in Alzheimer's disease.

Journal: NPJ dementia

In common: cellular / molecular, 3 references

[2] doi:10.1038/s41598-026-45990-4 [code]

Multi-platform profiling reveals host- and cell -type-specific pseudorabies virus gene expression.

Journal: Scientific reports

In common: other condition, cellular / molecular, 2 references

[3] doi:10.1080/19336896.2026.2710965

Epigenetic changes associated with the progression of prion disease in Syrian hamsters (<i>Mesocricetus auratus</i>).

Journal: Prion

In common: other condition, cellular / molecular, 3 references

[4] doi:10.1016/j.stemcr.2026.103012

Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development.

Journal: Stem cell reports

In common: cellular / molecular, 3 references

[5] doi:10.1038/s44318-026-00768-2 [code]

The H3K36me3 methyltransferase SETD2 contributes to PAF1C interactions with RNA Pol II and is required for neuronal differentiation.

Journal: The EMBO journal

In common: 2 references

[6] doi:10.1016/j.isci.2026.117017

Across species identification of genes bridging neurological and reproductive functions in mammals.

Journal: iScience

In common: cellular / molecular, 3 references

[7] doi:10.1016/j.isci.2026.116188 [code]

Genetic inactivation of Translin/Trax RNase disrupts miRNAs, hippocampal synaptic plasticity, and memory.

Journal: iScience

In common: cellular / molecular, 3 references

[8] doi:10.1080/19490976.2026.2693397 [code]

Gut <i>Proteobacteria</i> glycine metabolism regulates neuroplasticity, motivation, and reinstatement of cocaine self-administration in mice.

Journal: Gut microbes

In common: other condition, cellular / molecular, 2 references

[9] doi:10.1038/s43856-026-01510-z [code]

Mapping genetic convergence across brain structure, mental health, and cardiometabolic disease.

Journal: Communications medicine

In common: other condition, 2 references

[10] doi:10.1038/s41593-026-02367-0 [code]

A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes.

Journal: Nature neuroscience

In common: cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.