Bovine leukemia virus, a versatile agent with various pathogenic effects in various animal species.

The bovine leukemia virus is the etiological agent of a chronic lymphatic leukemia in cows, sheep, and goats. The same virus seems to induce a kind of wasting disease in experimentally infected rabbits. Antibodies to highly purified bovine leukemia viral Mr 51,000 glycoprotein and Mr 24,000 protein cross-react with human T-lymphotropic virus III/lymphadenopathy-associated virus antigens present in cultured lymphocytes of African patients suffering from acquired immune deficiency syndrome. Bovine leukemia virus has many structural and functional characteristics in common with the human T-lymphotropic viruses. The most striking feature of these retroviruses is the existence of a long open reading frame located at the 3' side of the provirus between the right end of the 3' side of env gene and the left end of the long terminal repeat. It is believed that the long open reading frame protein product acts in trans upon a number of genes to account for the biological effects of the virus.

Effect of tRNA pool balance on rate and uniformity of elongation during translation of fibroin mRNA in a reticulocyte cell-free system.

Unsuccessful attempts to synthesize complete fibroin chains in vitro were previously made in heterologous cell-free system [3]. In the present work, we succeeded to obtain complete translation of purified fibroin mRNA in a rabbit reticulocyte lysate. Whilst this work was being completed [1], similar results were published by Lizardi et al. [4]. The synthesis of full-sized molecules of fibroin (M.W. 360,000) was achieved by adding tRNA from the posterior silk gland to the cell-free system. With tRNA from other sources, both the translation rate and the amount of complete fibroin chains dropped. This effect of tRNA is situated at the elongation levels. Analysis of cell-free synthesized products by polyacrylamide gel electrophoresis shows that smaller discrete polypeptides are accumulated after 120 minutes of incubation. These polypeptides correspond to growing fibroin chains. This pattern of translation products suggests that elongation might decelerate at specific sites of the fibroin mRNA. These results show that a tRNA pool adjusted to mRNA codon frequency is required to obtain the maximal average elongation rate. A stochastic model based on random acceptance of tRNA at the ribosomal A site for the codon-anticodon recognition process can explain this phenomenon. It can also explain the occurrence of the unfinished discrete fibroin polypeptides during in vitro translation.

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.

Bovine leukaemia virus and enzootic bovine leukosis.

Infection of bovines with bovine leukaemia virus (BLV) manifests itself in either of two ways: 30-70% of carriers develop persistent lymphocytosis (PL), with the viral genome integrated at a large number of different sites in the DNA of the affected B-lymphocytes, without causing any chromosomal abnormalities. Only 0,1-10% of carriers develop lymphoid tumours, which also consist of B-lymphocytes. In contrast to PL, however, they are of mono- or oligoclonal origin in terms of the integration site, which is characteristic for each tumour. All cells contain one or more copies of the viral genome, chromosomal aberrations are common and if deletions are present they are invariably found in the 5'-half of the virus DNA sequence. In both types of affected cells transcription is repressed in vivo, but transient virus production can be induced in vitro and detected by means of syncytia induction or haemagglutination. In vivo production of virus in some unknown cell is suggested by the presence of high antibody titres in infected animals, especially against the envelope glycoprotein gp51. This can be detected by various techniques such as immunodiffusion, radioimmune assay or ELISA. Monoclonal antibodies against gp51 have revealed 8 epitopes, 3 of which are recognized by neutralizing antibodies and one by a cytolytic antibody. The BLV genome, about 9 kb in size, have been cloned, and some of the information obtained on its molecular structure and function is discussed. It codes for at least 4 non-glycosylated and 2 glycoproteins. Of special interest is the recently discovered serological relationship between some of the non-glycosylated proteins and those of the human T-cell leukaemia virus. The functional role of BLV in leukaemogenesis is largely unknown. The presence of the viral genome seems to be necessary for the maintenance of the transformed state, but not its continuous expression nor an LTR-mediated promotion of transcription of cellular genes. No oncogene is carried by the virus. Although bovine leukosis is not of major economic importance, its eradication is desirable and feasible in countries with a relatively low incidence, by means of testing and elimination. For endemic situations vaccination would be preferable, and distinct possibilities exist for the development of gp51 based vaccines.