IN-VIVO DYNAMICS OF EQUINE INFECTIOUS-ANEMIA VIRUSES EMERGING DURING FEBRILE EPISODES - INSERTIONS DUPLICATIONS AT THE PRINCIPAL NEUTRALIZING DOMAIN/

Equine infectious anemia virus (EIAV) is a good model for studying mec hanisms generating escaped retrovirus variants, We previously sequence d the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virul ent EIAV strain V70, The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. I n this study, we further characterized the PND of virus isolates seque ntially recovered during 22 febrile episodes in seven horses newly inf ected with V70 or one of the V70-derived variants. Sequencing of 70 cD NA clones derived from the 22 episodes confirmed the generation of var ious new viral quasispecies with insertions/duplications in the PND. A lthough the insertion/duplication sequences in a total of 92 cDNA clon es were extensively heterogeneous, we hypothesized that all the insert ions/duplications occurred during reverse transcription from viral gen omic RNA to minus strand DNA. The insertions/duplication regions were derived from a part of the I)ND sequence, which consisted of five smal l units, These small units, some with various substitutions and/or del etions, were also generated, especially in regions with insertions/dup lications. Of particular note was that all these virus variants, excep t for two cDNA variants, were generated by essentially four different duplication pathways, Thus. these results extend the significance of i nsertions/duplications in the PND to the novel generation of EIAV in v ivo during febrile episodes.