Enhancement of equine infectious anemia virus virulence by identification and removal of suboptimal nucleotides

Pathogenicity was reportedly restored to an avirulent molecular clone of equine infectious anemia virus (EIAV) by substitution of 3′ sequences from the pathogenic variant strain (EIAVPV). However, the incidence of disease in horses/ponies was found to be significantly lower (P = 0.016) with the chimeric clone (EIAVUK) than with EIAVPV. This was attributable to 3′ rather than 5′ regions of the proviral genome, where EIAVUK differs from the consensus EIAVPV sequence by having a 68-bp duplication in the 3′ LTR and arginine (R103) rather than tryptophan (W103) at position 103 in the second exon of rev. In EIAVUK recipients the duplication was rapidly eliminated and R103 replaced by W103 in the viral population. Furthermore, removal of the 3′ variant sequences from EIAVUK (EIAVUK3) resulted in an equivalent (P = 0.013) disease potential in Equus caballus to EIAVPV. The 68-bp duplication and/or R103 may limit peak viral RNA accumulation during acute infection.