An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family

BACKGROUND: Equine infectious anemia virus (EIAV), a lentivirus that infects horses, has been utilized as an animal model for the study of HIV. Furthermore, the disease associated with the equine lentivirus poses a significant challenge to veterinary medicine around the world. As with all lentiviruses, EIAV has been shown to have a high propensity for genomic sequence and antigenic variation, especially in its envelope (Env) proteins. Recent studies have demonstrated Env variation to be a major determinant of vaccine efficacy, emphasizing the importance of defining natural variation among field isolates of EIAV. To date, however, published EIAV sequences have been reported only for cell-adapted strains of virus, predominantly derived from a single primary virus isolate, EIAV(Wyoming )(EIAV(WY)). RESULTS: We present here the first characterization of the Env protein of a natural primary isolate from Pennsylvania (EIAV(PA)) since the widely utilized and referenced EIAV(WY )strain. The data demonstrated that the level of EIAV(PA )Env amino acid sequence variation, approximately 40% as compared to EIAV(WY), is much greater than current perceptions or published reports of natural EIAV variation between field isolates. This variation did not appear to give rise to changes in the predicted secondary structure of the proteins. While the EIAV(PA )Env was serologically cross reactive with the Env proteins of the cell-adapted reference strain, EIAV(PV )(derivative of EIAV(WY)), the two variant Envs were shown to lack any cross neutralization by immune serum from horses infected with the respective virus strains. CONCLUSION: Taking into account the significance of serum neutralization to universal vaccine efficacy, these findings are crucial considerations towards successful EIAV vaccine development and the potential inclusion of field isolate Envs in vaccine candidates.