Sequence analysis of the equid herpesvirus 2 chemokine receptor homologues E1, ORF74 and E6 demonstrates high sequence divergence between field isolates.

The research explores the genetic variability of equid herpesvirus 2 (EHV-2), focusing particularly on three specific cellular receptors, E1, ORF74, and E6. The study found high genetic divergence among different field isolates of the virus, suggesting that their external domains are less tolerant of mutations that could affect their function.

Detailed study of EHV-2

• The study delved into the genetic analysis of EHV-2, a virus that belongs to the subfamily Gammaherpesvirinae. This virus encodes cellular seven-transmembrane receptors (7TMR), specifically open reading frames (ORFs) E1, ORF74, and E6. These decoded receptors show some semblance to cellular chemokine receptors.
• The receptors ORF74 and E6 are part of gammaherpesvirus-conserved 7TMR gene families, while E1 is unique to EHV-2.

Variability in EHV-2 7TMRs

• To understand the genetic variability of these receptors, the researchers sequenced EHV-2 7TMRs from different equine gammaherpesvirus isolates.
• In addition, a region of gB, another chemokine receptor gene, was sequenced to provide comparative data.
• The resultant data revealed six ‘genogroups’ for receptor E1 and four for ORF74. The difference in the amino acid sequence between these groups ranged from approximately 10-38% for E1 and 11-27% for ORF74.
• Contrarily, receptor E6 showed high conservation with only two genogroups identified.

Negative Selective Pressure and Mutation Tolerance

• Further analysis showed the highest variation in the N-terminal domains and other extracellular regions.
• The study indicates a predominance of negative selective pressure on these EHV-2 7TMRs, suggesting its role in maintaining functionally important residues of the virus. However, some evidence was found pointing towards positive selection at some sites.
• Supporting this, the data indicates that the transmembrane and cytoplasmic domains of these receptors are less mutable, suggesting their critical role in the functional integrity of the virus.

Recombination between Different EHV-2 Strains

• The sequence data showed no evidence of genetic linkage between the different genogroups of gB, E1, ORF74, and E6 chemokine receptors.
• This finding points towards frequent intergenic recombination between the various EHV-2 strains, enhancing the virus’s genetic diversity and potential evolution rate.