Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors.

This research indicates that Equid herpesvirus type 4 (EHV-4), similarly to the related EHV-1, uses MHC-I molecules as receptors for cellular entry, potentially making most horses susceptible to infection. It also suggests that a key factor in this process is the presence of the amino acid alanine at position 173 (A173) in MHC-I molecules.

Understanding Cellular Entry Strategies of EHV

• The study demonstrates that Equid herpesvirus type 4 (EHV-4), like its relative EHV-1, uses a specific strategy to infiltrate cells. This strategy involves targeting MHC-I (major histocompatibility complex class I) molecules as entry receptors.
• The researchers confirmed the usage of this strategy in equine in vitro cell cultures and also in mouse mast cell tumor (P815) cells, which had been genetically modified or ‘transfected’ with equine MHC-I genes.

Role of MHC Molecules in Viral Entry

• A key discovery relates to the importance of a specific MHC-I molecule variant. Specifically, the presence of the amino acid Alamime (denoted A173) at a specific location (position 173) in MHC-I molecules seems to be crucial for the virus to gain entry into cells.
• The researchers observed that when other amino acids replaced alanine at this position, viral entry was either reduced or enhanced, depending on the specific amino acid that was present.
• However, not all MHC-I molecules with alanine at position 173 enabled viral entry, indicating that other, as yet unknown factors also play a role in the virus’ ability to invade cells.

Implications for Horse Populations

• The findings suggest that EHV-1 and EHV-4 acquired the ability to bind to MHC-I molecules from their common ancestor. The predominance of alanine at position 173 among MHC-I molecules in horses indicates that most horse hereditary types might be susceptible to these viruses.
• However, there are still questions to be answered. For instance, certain MHC-I genes carrying the A173 trait did not allow for viral entry in the modified P815 cells, underscoring the complexity of virus-cell interaction and the potential for future research.