Experimental strategy. Twelve sheep were infected by direct inoculation of a cloned BLV provirus. Six animals (top) were infected with the leukemogenic BLV infectious molecular clones pBLV344, pBLVTax106+293 and pBLVA60V (2 animals per clone). These molecularly cloned viruses induce leukemias in almost all infected animals. Six additional sheep (bottom) were infected with the infectious, but attenuated, cloned viruses pBLVCRX3, pBLVIG4 and pBLVCRE3X  (2 animals per clone). All 12 experimentally infected sheep seroconverted and developed persistent infection. For each animal, blood samples were prospectively collected by jugular venipuncture and prepared for analyses at the date of seroconversion, 3 days before, 3 and 50 days after, and 240 days after experimental infection. All animals infected with leukemogenic viruses were investigated prior to tumor onset. The 2 groups of infected sheep were compared for BLV replication by using quantitative analyses of circulating proviral loads, reverse-transcription (RT) events, RT-dependent genetic variability, clonal expansion, and somatic mutations.