RECOMBINANT FELINE LEUKEMIA-VIRUS GENES DETECTED IN NATURALLY-OCCURRING FELINE LYMPHOSARCOMAS

Using a polymerase chain reaction strategy aimed at detecting recombin ant feline leukemia virus (FeLV) genomes with 5' env sequences origina ting from an endogenous source and 3' env sequences resulting from FeL V subgroup A (FeLV-A), we detected recombinant proviruses in approxima tely three-fourths of naturally occurring thymic and alimentary feline lymphosarcomas (LSAs) and one-third of the multicentric LSAs from cat s determined to be FeLV capsid antigen positive by immunofluorescence assay. In contrast, only 1 of 22 naturally arising FeLV-negative felin e LSAs contained recombinant proviruses, and no recombinant env gene w as detected in seven samples from normal tissues or tissues from FeLV- positive animals that died from other diseases. Four preferred structu ral motifs were identified in the recombinants; one is FeLV-B like (re cognizing that FeLV-B itself is a product of recombination between FeL V-A and endogenous env genes), and three contain variable amounts of e ndogenous-like env gene before crossing over to FeLV-A-related sequenc es: (i) a combination of full-length and deleted env genes with recomb ination at sites in the middle of the surface glycoprotein (SU), (ii) the entire SU encoded by endogenous-like sequences, and (iii) the enti re SU and approximately half of the transmembrane protein encoded by e ndogenous-like sequences. Additionally, three of the thymic tumors con tained recombinant proviruses with mutations in the vicinity of the ma jor neutralizing determinant for the SU protein. These molecular genet ic analyses of the LSA DNAs correspond to our previous results in vitr o and support the occurrence and association of viral recombinants and mutants in vivo in FeLV-induced leukemogenesis.