Differential pathogenicity of two feline leukemia virus subgroup A molecular clones, pFRA and pF6A

F6A a molecular clone of subgroup A feline leukemia virus (FeLV) is conside red to be highly infectious but weakly pathogenic. In recent studies with a closely related subgroup A molecular clone, FRA, we demonstrated high path ogenicity and a strong propensity to undergo recombination with endogenous FeLV (enFeLV), leading to a high frequency of transition from subgroup A to A/B. The present study was undertaken to identify mechanisms of FeLV patho genesis that might become evident by comparing the two closely related mole cular clones. F6A was shown to have an infectivity similar to that of FRA. when delivered as a provirus, Virus load and antibody responses were also s imilar, although F6A-infected cats consistently carried higher virus loads than FRA-infected cats. However, F6A-infected cats were slower to undergo d e novo recombination with enFeLV and showed slower progression to disease t han FRA-infected rats. Tumors collected from nine pF6A- or pFA-inoculated c ats expressed lymphocyte markers for T cells (seven tumors) and B cells (on e tumor), and non-T/B cells (one tumor). One cat with an A-to-A/C conversio n developed erythrocyte hypoplasia. Genomic mapping of recombinants from pF 6A- and pFRA-inoculated cats revealed similar crossover sites, suggesting t hat the genomic makeup of the recombinants did not contribute to increased progression to neoplastic disease, From these studies, the mechanism most L ikely to account for the pathologic differences between F6A and FRA is the lower propensity for F6A to undergo de novo recombination with enFeLV in vi vo. A lower recombination rate is predicted to slow the transition from sub group A to A/B and slow the progression to disease.