Evolutionary Patterns of the Proviral gp90 V3 to V5 Regions of Equine Infectious Anemia Virus Associated with Immune Selection in Progressors and Nonprogressors

The aim of this study was to determine the genomic evolutionary pattern of virulent equine infectious anemia virus (EIAV) during persistent infection. The evolutionary dynamics of proviral genomes were examined by challenging an EIAV seronegative equine (pony 1) and three EIAV vaccinated equines (ponies 4, 7, and 8) with the Chinese virulent strain EIAV-L. Ponies 1 and 7 succumbed to disease and were called progressors, while ponies 4 and 8 lacked clinical symptoms and were considered nonprogressors. Sequences spanning the V3, V4, and V5 hyper-variable regions of the EIAV-L envelope gp90 gene were sequenced from each pony as evolutionary markers of the provirus. The proviral genome of the EIAV-L inoculum evolved during persistent infection and displayed different patterns between EIA progressors and nonprogressors. Inoculum-like variants were isolated from nonprogressors during persistent infection, but only from progressors during acute infection. Variant mutations from nonprogressors were dispersed throughout the sequenced region, while those from progressors were predominantly localized to V3. Humoral immunity and virus variant population selection analyses indicated that immune selection was positive in chronically infected progressors and weak in nonprogressors. In-frame stop codons were frequently localized to a defect “hot spot”. The high number of defective variants in nonprogressors may promote disease survival.