Complex Interactions between the Major and Minor Envelope Proteins of Equine Arteritis Virus Determine Its Tropism for Equine CD3⁺T Lymphocytes and CD14⁺Monocytes

Abstract

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.

Sequence analysis of minor protein genes of equine arteritis virus during persistent infection

“…This position is a part of the ectodomain of the GP4 protein and was previously described as a variable (3). As GP4 is one of the proteins important for the determination of viral tropism, stable substitution of this nature on the exposed part of this protein could be the result of adaptive pressure (11).…”

Development and use of a polarized equine upper respiratory tract mucosal explant system to study the early phase of pathogenesis of a European strain of equine arteritis virus

“…In the present study, both T-lymphocytes and cells of the monocyte/macrophage lineage were found to be infected with EAV. Other studies have also demonstrated that EAV can infect CD3 + T lymphocytes in PBMC in vitro [25,26]. …”

Evidence thatIn VitroSusceptibility of CD3+T Lymphocytes to Equine Arteritis Virus Infection Reflects Genetic Predisposition of Naturally Infected Stallions To Become Carriers of the Virus

“…Subsequently, peripheral blood mononuclear cells (PBMCs) were collected from long-term carrier (n ϭ 7) and noncarrier (n ϭ 7) stallions ( Table 1). The susceptible or resistant phenotype of each animal was defined by dual-color flow cytometric analysis of in vitro EAV-infected CD3 ϩ T lymphocytes as described previously (6). Interestingly, CD3…”

“…The percentage of the CD3 ϩ T lymphocyte population that was susceptible to EAV infection ranged from 4% to 17% among carrier stallions. As previously described, a majority of the CD3 ϩ T lymphocytes infected which is associated with CD3 ϩ T cell susceptibility, is highlighted in yellow, as described elsewhere (6). Each haplotype is highlighted with a different color.…”