UNIQUE LONG TERMINAL REPEAT U3 SEQUENCES DISTINGUISH EXOGENOUS JAAGSIEKTE SHEEP RETROVIRUSES ASSOCIATED WITH OVINE PULMONARY-CARCINOMA FROMENDOGENOUS LOCI IN THE SHEEP GENOME

Ovine pulmonary carcinoma (OPC) is a contagious lung cancer of sheep t hat is presumed to be caused by an exogenous retrovirus of sheep, jaag siekte sheep retrovirus (JSRV). The sheep genome carries 15 to 20 copi es of endogenous sheep retrovirus (ESRV) loci that hybridize to JSRV D NA probes, In order to clarify the etiologic roles of ESRV and an exog enous JSRV-like retrovirus (exJSRV) in OPC, we assessed sequence diffe rences between ESRV and JSRV, Molecular characterization of six ESRV l oci revealed restriction sites specific for JSRV, Nucleotide sequences of ESRVs from sheep of different breeds were similar to those of JSRV in structural genes but divergent in U3, Therefore, primers specific for the U3 sequences of exJSRV were designed for use in the PCR Of 13 tumor DNAs tested by PCR with these exogenous-virus U3 primers, 8 prod uced DNA fragments that hybridized with the JSRV gag probe, but neithe r lung DNAs from healthy sheep nor DNAs from nontumor tissues of disea sed sheep produced similar DNA fragments, exJSRV PCR products from tum or DNAs of sheep with OPC from three continents had restriction profil es similar to each other but different from those of ESRVs upon digest ion with EcoRI, HindIII, NdeI, KpnI, and ScaI. These exJSRVs could be classified into two genotypes according to U3 sequences and restrictio n profiles, U3 sequences of exJSRV proviruses in tumors strongly resem bled those of JSRV but differed from those of ESRVs, suggesting that e xJSRVs, rather than ESRVs, are primarily associated with oncogenesis i n OPC.