Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer

Bovine leukaemia virus (BLV) is the etiological agent of chronic lymphatic leukaemia/lymphoma in cows, sheep and goats. Infection without neoplastic transformation was also obtained in pigs, rhesus monkeys, chimpanzees, rabbits and observed in capybaras and water-buffaloes. Structurally and functionally, BLV is a relative of human T lymphotropic viruses 1 and 2 (HTLV-I and HTLV-II) In humans, HTLV-I induces a T-cell leukaemia and its type 2 counterpart has been found in dermatopathic lymphadenopathy, hairy T-cell leukaemia and prolymphocytic leukaemia cases. At variance with HTLV-I, BLV has not been associated with neurological diseases of the degenerative type. Bovine leukaemia virus, HTLV-I and HTLV-II show clearcut sequence homologies. The pathology of the BLV-induced disease, most notably the absence of chronic viraemia, a long latency period and lack of preferred proviral integration sites in tumours, is similar to that of adult T-cell leukaemia/lymphoma induced by HTLV-I. The most striking feature of these three naturally transmitted leukaemia viruses is the X region located between the env gene and the long terminal repeat (LTR) sequence. The X region contains several overlapping long open reading frames. One of them, designated XBL-I, encodes a trans-activator function capable of increasing the level of gene expression directed by BLV-LTR and most probably is involved in "genetic instability" of BLV-infected cells of the B cell lineage. The "genetic instability" renders the infected cell susceptible to move, along a number of stages, towards full malignancy. Little is known about these events and their causes; we present some theoretical possibilities. Bovine leukaemia virus infection has a worldwide distribution. In temperate climates, the virus spreads mostly via iatrogenic transfer of infected lymphocytes. In warm climates and in areas heavily populated by haematophagous insects, there are indications of insect-borne propagation of the virus.