Transcription of bovine leukemia virus in peripheral blood cells obtained during early infection in vivo

Bovine leukemia virus (BLV) is transcriptionally silent in most circulating peripheral blood mononuclear cells (PBMCs) of animals with well-established infections. Using PBMCs from a newly infected sheep, we asked whether viral transcription proceeded differently during the initial months of infection, when the prevalence of BLV-infected cells and the host's immunological response change markedly. Shortly after being injected with BLV, the animal displayed a characteristic, transient increase in PBMCs that transcribed BLV when cultured. Even when transcriptionally competent PBMCs were most prevalent (1.2%), only rare cells in the circulation (1 in 50 000) contained enough BLV transcripts to be identified readily by in situ hybridization. However, at one point several weeks later, some PBMCs appeared to contain small amounts of BLV RNA as soon as they had been purified from blood. Throughout this period, BLV-transcribing PBMCs greatly outnumbered virus-producing cells, which were counted using a new infectious centers assay. Its viscous medium reduced cell to cell contact among PBMCs, enabling increased detection of BLV-producing cells at a time when virus-specific killer cells might be active. Early infection was polyclonal, and most infected PBMCs transcribed BLV upon being cultured. By 2 months after infection, provirus-containing cells were as abundant as they had been earlier, but few cells transcribed BLV. These results suggest that BLV-infected cells are more easily stimulated to transcribe the provirus and produce infectious virus during the early months of a new infection.