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

## TL;DR

This study compares how human, bovine, and equine cells respond to alphaherpesvirus infections, revealing both shared and unique gene activity patterns.

## Contribution

The study provides a cross-species comparative framework of transcriptional responses to three alphaherpesviruses using RNA sequencing.

## Key findings

- Orthologous genes and pathways like translation, rRNA processing, and TNF-alpha signaling are differentially regulated across species.
- The 2 h post-infection timepoint shows the most commonly enriched pathways among all three species.
- BHV-1 and EHV-1 infections share more enriched pathways at 6 h and 9 h post-infection than with HSV-1.

## 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.