The FeLV-945 LTR confers a replicative advantage dependent on the presenceof a tandem triplication

Feline leukemia virus (FeLV), like other naturally occurring retroviruses, is characterized by a high degree of genetic diversity. FeLV-945 is a natur al isolate derived from non-B-cell non-T-cell lymphomas classified anatomic ally as multicentric. FeLV-945 exhibits a unique structural motif in the LT R composed of a 21-bp tandem triplication downstream of a single copy of en hancer. Tnf unique FeLV-945 LTE is precisely conserved among eight independ ent multicentric lymphomas collected in a geographic cluster. Previous stud ies using reporter gene constructs predict that the FeLV-945 LTR would conf er a replicative advantage on the virus that contains it, particularly in p rimitive hematopoietic cells. Such an advantage may account for the precise conservation of the unique LTR sequence. To test that prediction, a set of recombinant, infectious FeLVe was developed that are isogenic other than t he presence of the FeLV-945 LTR or mutations of it. Replication assays show that the FeLV-945 LTR confers a distinct growth advantage in K-562, FEA, a nd 3201 cells and implicate the 21-bp triplication in that function. Replac ement of two copies of the triplicated element with random sequence greatly diminished the replicative capacity, thus implicating the triplicated elem ent itself in LTR function. The 21-bp triplication was shown to contain spe cific nuclear protein binding sites, which may account for the selective pr essure to conserve the sequence. (C) 1999 Academic Press.