Complex interactions between the major and minor envelope proteins of equine arteritis virus determine its tropism for equine CD3⁺ T lymphocytes and CD14⁺ monocytes

Extensive cell culture passage of the virulent Bucyrus (VB) strain of equine arteritis virus (EAV) to produce the modified live virus (MLV) vaccine strain has altered its tropism for equine CD3⁺ T lymphocytes and CD14⁺ monocytes. The VB strain primarily infects CD14⁺ monocytes and a small subpopulation of CD3⁺ T lymphocytes (predominantly CD4⁺ T lymphocytes), as determined by dual-color flow cytometry. In contrast, the MLV vaccine strain has a significantly reduced ability to infect CD14⁺ monocytes and has lost its capability to infect CD3⁺ T lymphocytes. Using a panel of five recombinant chimeric viruses, we demonstrated that interactions among the GP2, GP3, GP4, GP5, and M envelope proteins play a major role in determining the CD14⁺ monocyte tropism while the tropism for CD3⁺ T lymphocytes is determined by the GP2, GP4, GP5, and M envelope proteins but not the GP3 protein. The data clearly suggest that there are intricate interactions among these envelope proteins that affect the binding of EAV to different cell receptors on CD3 ⁺ T lymphocytes and CD14⁺ monocytes. This study shows, for the first time, that CD3⁺ T lymphocytes may play an important role in the pathogenesis of equine viral arteritis when horses are infected with the virulent strains of EAV.