Comprehensive Analysis of Equid Herpesvirus Recombination: An Insight Into the Repeat Regions

High-throughput sequencing of genomes has expanded our knowledge of the Alphaherpesvirinae, a widely extended subfamily of DNA viruses that recombine to increase their genetic diversity. It has been ac-knowledged that equid herpesvirus 1 (EHV-1) and equid herpesvirus 4 (EHV-4), two alphaherpesviruses with an economic impact on the horse industry, can recombine. This work aimed to analyze interspe-cific recombination between all equid alphaherpesvirus species, using genomes of EHV-1, EHV-3, EHV-4, EHV-6, EHV-8, and EHV-9 available in GenBank. 14 events of recombination by RDP4 and Simplot be-tween EHV-1 x EHV-4, EHV-1 x EHV-9, EHV-8 x EHV-1, and EHV-8 x EHV-9 were identified. Ten out of 14 events involved ORF64, a double-copy gene located at the repeat regions that codifies for the infected cell protein 4 (ICP4). Among the ICP4, recombination can be found between EHV-1 X EHV-9, EHV-8 X EHV-9, and EHV-1 X EHV-4, the former affects zebra-borne genotypes, a type of EHV-1 that infect wild equids, and the latter match with previous breakpoints reported in fields isolates. Consequently, these findings strongly suggest that ICP4 is a hotspot for recombination. This work describes novel recombi-nation events and is the first genome-wide recombination analysis using all available equid alphaher-pesvirus species genomes. (c) 2023 Elsevier Inc. All rights reserved.

Automated summary

This study analyzed interspecific recombination events between different equine alphaherpesvirus species and identified 14 recombination events involving important gene ORF64. The results suggest that infected cell protein 4 (ICP4) is a hotspot for recombination in equine alphaherpesviruses.