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Journal of virology2025; 99(12); e0158925; doi: 10.1128/jvi.01589-25

Equine histones are mobilized within equid alphaherpesvirus 1 (EHV1) replication compartments.

Abstract: Equid alphaherpesvirus 1 (EHV1) is a DNA virus that causes severe disease in equids. Some strains are neurotropic and cause disease in the central nervous system, whereas others are non-neurotropic and can cause negative reproductive outcomes. Mechanisms governing EHV1 pathotype are not understood. However, EHV1 pathotypes have different infection efficiencies and replication kinetics in various cell types. They are also differentially susceptible to epigenetic inhibitors. Aside from this observation little is known about EHV1 chromatin or how its regulation influences infection. To build knowledge of EHV1 chromatin, we characterized equine histone mobility during EHV1 infection of equine cells using fluorescence recovery after photobleaching. We show that non-neurotropic or neurotropic EHV1 equally mobilized canonical (H2A, H2B, H3.1, and H4) and variant (H2A.B, H2A.Z, H2A.X, macroH2A, and H3.3) core and linker H1.2 histones. EHV1 mobilized dynamic histone populations by increasing their free pools and fast chromatin exchange. With the exception of H2A.B, all histones were most mobile within EHV1 replication compartments where EHV1 chromatin is enriched. Such mobility is consistent with highly dynamic viral chromatin. Distinct histone mobilities within EHV1- or infected-cell chromatin also indicate that different mechanisms regulate either chromatin. EHV1 mobilization of histones is similar to that reported for herpes simplex virus 1 (HSV1). This unique chromatin regulatory strategy is thus conserved among alphaherpesviruses in the and genera. Importantly, this conservation highlights histone mobilization as a robust chromatin regulatory strategy to promote viral genome accessibility during infection of evolutionarily distinct species.IMPORTANCEDNA viruses are subject to chromatin regulation of their gene expression. Understanding how viruses overcome genome silencing or promote the expression of their genes is important to understand how viruses take over host cells and establish productive infection. We show that EHV1 robustly mobilizes histones within nuclear domains enriched in viral chromatin. Histone mobilization would destabilize chromatin and is consistent with the assembly of dynamic or unstable EHV1 nucleosomes. Histone mobilization is a phenomenon first described for herpes simplex virus 1 (HSV1). Thus, destabilization of chromatin by mobilizing histones is conserved across the and genera of alphaherpesviruses. Although this unique chromatin regulatory approach is conserved, we identified differences in histone mobilization by either virus. Knowledge of how alphaherpesviruses mobilize histones during the infection of evolutionarily distinct species will increase our understanding of viral chromatin regulation and support the development of novel therapeutics to silence viral genomes.
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Publication Date: 2025-11-25 PubMed ID: 41288450PubMed Central: PMC12724232DOI: 10.1128/jvi.01589-25Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Equid alphaherpesvirus 1 (EHV1), a virus affecting horses, actively mobilizes histone proteins within its replication sites to alter viral chromatin structure, facilitating viral gene expression and efficient infection. This histone mobilization is a conserved strategy shared with related herpesviruses, highlighting a critical mechanism in viral genome regulation.

Background and Research Goals

  • EHV1 is a DNA virus causing serious diseases in horses, including neurological disorders and reproductive problems.
  • Different EHV1 strains (neurotropic vs non-neurotropic) show variable infection efficiency and response to epigenetic inhibitors, but the exact mechanisms behind these differences are unclear.
  • DNA viruses like EHV1 are regulated by chromatin, which influences gene expression, but little is known about EHV1’s chromatin structure or regulation.
  • The research aimed to understand how EHV1 affects histone mobility during infection, which could indicate chromatin dynamics and viral genome accessibility.

Methodological Approach

  • The study used fluorescence recovery after photobleaching (FRAP) to analyze the mobility of various histone proteins in equine cells infected with EHV1.
  • They examined both canonical histones (H2A, H2B, H3.1, and H4) and variant histones (H2A.B, H2A.Z, H2A.X, macroH2A, and H3.3), as well as linker histone H1.2.
  • Comparisons were made between infected cell chromatin and EHV1 replication compartments, which are nuclear domains enriched with viral DNA.

Key Findings

  • Both neurotropic and non-neurotropic EHV1 strains similarly increased the mobility of core and linker histones within infected cells.
  • Histone mobilization involved increasing the free (unbound) histone pool and enhancing rapid chromatin exchange dynamics.
  • With the exception of the variant H2A.B histone, all tested histones were most mobile within EHV1 replication compartments, suggesting viral chromatin is highly dynamic.
  • Distinct histone mobilities between viral and host chromatin indicate different regulatory mechanisms operate in viral vs cellular chromatin contexts.

Comparison With Other Alphaherpesviruses

  • Histone mobilization during infection was previously described in herpes simplex virus 1 (HSV1), a related alphaherpesvirus.
  • The current study shows that this chromatin regulatory strategy is conserved between EHV1 and HSV1, despite their infection of evolutionarily distinct species (horses vs humans).
  • This conservation suggests histone mobilization is a robust viral strategy for promoting genome accessibility and efficient viral gene expression.
  • Despite the overall similarity, some differences in histone mobilization between EHV1 and HSV1 were noted.

Significance and Implications

  • Understanding histone mobilization helps reveal how alphaherpesviruses overcome chromatin-mediated repression to establish productive infection.
  • Mobilized histones likely destabilize nucleosomes on viral DNA, facilitating rapid transcription and replication of viral genes.
  • Insights into this unique chromatin regulation could inform development of novel antiviral therapies aimed at re-establishing viral genome silencing.
  • Knowledge of viral chromatin dynamics in different host species enhances our broader understanding of virus-host interactions and viral pathogenesis.

Cite This Article

APA
Conn KL. (2025). Equine histones are mobilized within equid alphaherpesvirus 1 (EHV1) replication compartments. J Virol, 99(12), e0158925. https://doi.org/10.1128/jvi.01589-25

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 99
Issue: 12
Pages: e0158925
PII: e01589-25

Researcher Affiliations

Conn, Kristen L
  • Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

MeSH Terms

  • Animals
  • Horses
  • Histones / metabolism
  • Histones / genetics
  • Herpesvirus 1, Equid / physiology
  • Herpesvirus 1, Equid / genetics
  • Virus Replication
  • Chromatin / metabolism
  • Herpesviridae Infections / virology
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / metabolism
  • Cell Line
  • Horse Diseases / virology
  • Horse Diseases / metabolism
  • Viral Replication Compartments / metabolism

Conflict of Interest Statement

The author declares no conflict of interest.

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Citations

This article has been cited 1 times.
  1. Schmitz M, Neugebauer E, Full F, Conn KL. Cross-Species Analysis of Transcriptomic Response to Alpha-Herpesvirus Infection in Human, Bovine and Equine Cells. Int J Mol Sci 2026 Jan 27;27(3).
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