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 (EIAV(PV)). However, the incidence of disease in horses/ponies was found to be significantly lower (P = 0.016) with the chimeric clone (EIAV(UK)) than with EIAV(PV). This was attributable to 3' rather than 5' regions of the proviral genome, where EIAV(UK) differs from the consensus EIAV(PV) sequence by having a 68-bp duplication in the 3' LTR and arginine (R(103)) rather than tryptophan (W(103)) at position 103 in the second exon of rev. In EIAV(UK) recipients the duplication was rapidly eliminated and R(103) replaced by W(103) in the viral population. Furthermore, removal of the 3' variant sequences from EIAV(UK) (EIAV(UK3)) resulted in an equivalent (P = 0.013) disease potential in Equus caballus to EIAV(PV). The 68-bp duplication and/or R(103) may limit peak viral RNA accumulation during acute infection.
Cook
R Frank
RF
Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA. rfcook1@uky.edu
Cook
Sheila J
SJ
Berger
Sandra L
SL
Leroux
Caroline
C
Ghabrial
Nadia N
NN
Gantz
Marie
M
Bolin
Pamela S
PS
Mousel
Michelle R
MR
Montelaro
Ronald C
RC
Issel
Charles J
CJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000235:genetics; D002478:Cells, Cultured; D004859:Equine Infectious Anemia / Q000821:virology*; D015683:Gene Products, gag / Q000235:genetics; D015684:Gene Products, pol / Q000235:genetics; D006736:Horses; D004860:Infectious Anemia Virus, Equine / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D016415:Sequence Alignment; D020079:Terminal Repeat Sequences; D014364:Tryptophan / Q000235:genetics; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication
D015683:Gene Products, gag; D015684:Gene Products, pol; D014364:Tryptophan; D001120:Arginine