Figure 1.

Clinical course of bovine leukemia virus (BLV) infection. Primary infection: an infected cell (red) with a BLV integrated into the host chromosome (blue provirus) is transmitted into a new animal. During primary infection, the BLV provirus is expressed into viral particles (blue hexagon), which further infect B-cells (yellow). Active BLV replication is responsible for a “flu-like” syndrome, as observed during primary infection by HIV in humans. During persistent infection, provirus-carrying cells (red) expand mainly by mitosis, because of the presence of an active immune response. This phase extends for several months/years and is characterized by an immune dysregulation (e.g., overexpression of cytokines), as observed in HTLV associated myelopathy / tropical spastic paraparesis (HAM/TSP) subjects infected by human T-lymphotropic virus type 1 (HTLV-1). In about 30%–70% of animals, the number of infected cells in blood increases above normal levels of 10,000/mm³. During this persistent lymphocytosis phase, morbidity is characterized by weakness and opportunistic infections, as observed in chronic lymphocytic leukemia in human. Morbidity (e.g., mastitis) leads to a loss in milk production. In the tumor phase, a single infected cell undergoes genetic mutations (black) and forms a lymphoma within or outside lymph nodes, leading to the death of the animal. Typically, animals undergo sudden death from the hemorrhage of the spleen. Tumors can also occur directly in persistently infected animals without persistent lymphocytosis (PL). The frequency of tumors and clinical latency depend on herd prevalence. A typical picture is 10% death after three years in a herd having 50% BLV prevalence.