GENOMIC QUASI-SPECIES ASSOCIATED WITH THE INITIATION OF INFECTION ANDDISEASE IN PONIES EXPERIMENTALLY INFECTED WITH EQUINE INFECTIOUS-ANEMIA VIRUS

Equine infectious anemia virus (EIAV) provides a uniquely dynamic syst em in which to study the mechanism and role of genomic variation in le ntiviral persistence and pathogenesis. We have used a Shetland pony mo del of infection to investigate the association of specific long termi nal repeat (LTR) and env gene genomic sequences with the initiation of infection and the onset of disease. We analyzed viral RNA isolated fr om a pathogenic stock of virus (ELAV(PV)) and from plasma taken during the first disease episode from two ponies infected with EIAV(PV). Ove rall sequence variation within gp90 was low in EIAV(PV) and only sligh tly higher in plasma virus samples isolated from ponies during the fir st disease episode. However, a high proportion of mutations were local ized to the principal neutralizing domain in EIAV(PV) and to the princ ipal neutralizing domain and the gp90 hypervariable region in the two pony-derived samples. The rate of fixation of mutations was analyzed a nd determined to be approximately 4 x 10(-2) mutations per site per ye ar. Sequence diversity within the U3 region of the LTR was extremely l ow, which suggested that the previously reported hypervariability of t his region may be a consequence of selection for replication of ELAV i n different host cells. The predominant EIAV(PV) env and LTR sequences were used to construct chimeric viruses so that the contribution of t hese sequences to viral pathogenicity could be examined. The chimeras replicated in cultured equine monocytes to the same extent as the pare ntal nonpathogenic virus and did not cause disease in Shetland ponies by 120 days postinfection, suggesting that the EIAV genomic determinan ts of pathogenesis are complex.