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International journal of molecular sciences2026; 27(3); 1261; doi: 10.3390/ijms27031261

Cross-Species Analysis of Transcriptomic Response to Alpha-Herpesvirus Infection in Human, Bovine and Equine Cells.

Abstract: Comparative transcriptomics offers a powerful approach to elucidate host-virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species' cells infected with three alphaherpesviruses-herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)-to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection among the three species like pathways related to translation rRNA processing and TNF-alpha signalling. We find that the earliest sampled timepoint of infection, 2 h post infection (hpi), shows the most commonly enriched pathways among the three species compared to later timepoints. At 6 h and 9 h post infection, BHV-1- and EHV-1 infections have more in common with each other in terms of enriched pathways than with HSV-1 infections. Moreover, we provide a comprehensive analysis of temporal viral gene expression for all three herpesviruses. Together, these findings provide a comparative framework for understanding alphaherpevirus-host interactions and reveal both conserved core responses and species-specific transcriptional signatures. This work establishes a foundation for identifying broadly acting antiviral targets as well as virus-specific vulnerabilities that may inform host-directed therapies and cross-species disease management.
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Publication Date: 2026-01-27 PubMed ID: 41683687PubMed Central: PMC12898550DOI: 10.3390/ijms27031261Google Scholar: Lookup
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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.

Overview

  • This study compares how cells from humans, cattle, and horses respond to infection by different but related alphaherpesviruses at the gene expression level.
  • The research identifies both shared and unique cellular responses across species and viruses, offering insights into virus-host interactions and potential antiviral strategies.

Introduction to the Study

  • Alphaherpesviruses are a group of related viruses that infect different species: HSV-1 in humans, BHV-1 in cattle, and EHV-1 in horses.
  • Understanding host responses across species can reveal conserved mechanisms the viruses exploit or trigger and highlight species-specific pathways important for infection outcomes.
  • Comparative transcriptomics, the study of gene expression changes across species, helps elucidate these mechanisms but had not been systematically performed using matched cellular models for these viruses before.

Methodology

  • Researchers infected species-specific cells (human, bovine, and equine) with their respective alphaherpesvirus (HSV-1, BHV-1, and EHV-1).
  • RNA sequencing (RNA-seq) was used to measure changes in the mRNA levels of genes at multiple time points after infection (2 hours, 6 hours, and 9 hours post infection).
  • Comparisons were made across the different species to identify orthologous genes (genes in different species that evolved from a common ancestral gene) and pathways responding to infection.
  • Temporal viral gene expression was also analyzed to examine differences and similarities in viral activity over time.

Key Findings

  • Common Early Response: At the earliest timepoint (2 hours post-infection), many pathways were commonly enriched across all three species, indicating a conserved initial cellular response to alphaherpesvirus infection.
  • Pathways Involved: Shared responses involved pathways related to translation (protein synthesis), rRNA processing (important for ribosome function), and TNF-alpha signaling (a key inflammatory response).
  • Divergence Over Time: By 6 and 9 hours post-infection, the transcriptional responses diverged, with bovine and equine cells showing more similar pathway enrichment to each other than to human cells.
  • Species-Specific Responses: Some genes and pathways were regulated differently depending on the virus and the host species, highlighting unique host-virus dynamics.
  • Viral Gene Expression Dynamics: The study also mapped how viral genes progressed over time in infected cells, providing insight into viral life cycles and replication processes in different hosts.

Significance of the Research

  • Identifies core, conserved host responses that could serve as broad-spectrum antiviral targets effective against multiple alphaherpesviruses and hosts.
  • Sheds light on species-specific viral vulnerabilities which could inform tailored antiviral therapies for different animals, improving disease management across species.
  • Offers a valuable comparative framework for future research into alphaherpesvirus biology and host-pathogen interaction mechanisms.
  • Supports development of host-directed therapies that modulate the host response rather than targeting the virus directly, potentially reducing resistance.

Cite This Article

APA
Schmitz M, Neugebauer E, Full F, Conn KL. (2026). Cross-Species Analysis of Transcriptomic Response to Alpha-Herpesvirus Infection in Human, Bovine and Equine Cells. Int J Mol Sci, 27(3), 1261. https://doi.org/10.3390/ijms27031261

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 27
Issue: 3
PII: 1261

Researcher Affiliations

Schmitz, Mirko
  • Institute of Virology, Medical Center, University of Freiburg, 79104 Freiburg, Germany.
Neugebauer, Eva
  • Institute of Virology, Medical Center, University of Freiburg, 79104 Freiburg, Germany.
  • Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104 Freiburg, Germany.
  • Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Full, Florian
  • Institute of Virology, Medical Center, University of Freiburg, 79104 Freiburg, Germany.
  • German Consulting Laboratory for HSV and VZV, Medical Center, University of Freiburg, 79104 Freiburg, Germany.
Conn, Kristen L
  • Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

MeSH Terms

  • Animals
  • Cattle
  • Horses
  • Transcriptome
  • Humans
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / virology
  • Alphaherpesvirinae / genetics
  • Gene Expression Profiling
  • Host-Pathogen Interactions / genetics
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Bovine / genetics
  • Species Specificity
  • Cell Line
  • Herpesvirus 1, Equid / genetics

Grant Funding

  • BMBF 01KI2017 / Bundesministerium für Forschung, Technologie und Raumfahrt

Conflict of Interest Statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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