Transcriptional activation of bovine leukemia virus in blood cells from experimentally infected, asymptomatic sheep with latent infections

Abstract

Infection by bovine leukemia virus (BLV) is characterized by a long latency period, after which some individuals develop B-cell tumors. The behavior of BLV and related retroviruses during the latency period between initial infection and subsequent tumorigenesis is poorly understood. We used in situ hybridization to detect BLV transcripts in individual peripheral blood mononuclear cells from experimentally infected, asymptomatic sheep with latent infections. Viral RNA was not found in most peripheral blood cells that had been isolated as rapidly as possible from circulating blood, but it was present in rare cells. BLV RNA transcripts increased in a biphasic manner within a few hours after the blood cells were placed in culture. Exposure to fetal bovine serum was identified as the principal cause of this transcriptional activation, which occurred in fewer than 1 in 1,000 cells. Agents known to activate immune cells polyclonally caused a further increase in the number of cells containing BLV RNA within 8 h. In some cases, the numbers of viral transcripts within individual cells also increased. Thus, BLV is not detectably expressed in most resting lymphocytes circulating in the blood, but its transcription is activated by components of fetal bovine serum and can be augmented by molecules that mimic activation of immune cells. This activation, which might occur in lymphoid tissue during an immune response, may lead to the synthesis of viral regulatory proteins that are thought to initiate tumorigenesis through host cell genes.