In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease, bovine leukemia virus (BLV), belongs to the deltaretrovirus genus which also includes the related human T-lymphotropic virus type 1 (HTLV-1). This review summarizes current knowledge of this viral system, which is important as a model for leukemogenesis. Recently, the BLV model has also cast light onto novel prospects for therapies of HTLV induced diseases, for which no satisfactory treatment exists so far.

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Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

In bovine pathology, research performed between 1871 and 1877 by Siedam-grotzky was apparently the first attempt to study bovine leukosis (BL) and characterize it as a clinical entity. At the beginning of the 20th century, pathologists interested in this disease observed that BL is a herd disease of probable infectious origin. In 1957, Bendixen initiated an epidemiological study of BL in Denmark (Bendixen, 1963), and documented the existence of an enzootic disease [enzootic bovine leukosis (EBL)]. EBL is a chronic contagious disease that evolves over an extended period of time (1–8 years), with tumors eventually developing in only a small number of affected animals. He also defined a group of sporadic manifestations [sporadic bovine leukosis (SBL)], which are not contagious or linked to the presence of a virus.

Bovine Leukemia Virus

It has recently been shown by mass spectral analysis (Henderson et al., Proc. Natl. Acad. Sci. U.S.A. 80:339-343, 1983) that the p15gag protein of murine leukemia viruses contains a novel post-translational modification, an amino-terminal myristyl (tetradecanoyl) amide. In this report we show that p15gag is the only structural protein to contain this fatty acid. In addition, the gag precursor polyproteins of type B, C, and D retroviruses have been examined for the presence of myristic acid by metabolic labeling and immunoprecipitation studies. In a panel of mammalian type C retroviruses we found that the precursor polyprotein Pr65gag homologs, but not the glycosylated forms (gPr80gag homologs), were specifically labeled after a 5-min incubation of infected cells with [3H]myristic acid. The gag precursor polyprotein was also labeled in mouse mammary tumor virus and in Mason-Pfizer monkey virus, but Pr76gag of Rous sarcoma virus failed to incorporate [3H]myristate. Under similar conditions, [3H]palmitate was not found to be incorporated into any viral gag proteins. Thus, myristylation appears to be a common feature of mammalian type B, C, and D retroviruses but not of avian retroviruses.

In vivo modification of retroviral gag gene-encoded polyproteins by myristic acid.

This study demonstrates that the bovine leukemia virus (BLV) can infect in vitro cells of human, simian, bovine, canine, caprine, ovine, and bat origin. Cultures of these cells, cocultivated with BLV-infected cells or inoculated with cell-free BLV preparations, continuoously showed the presence of cells with the internal BLV antigen as well as BLV-induced syncytia. Virus replication was abundant and increased with passage in bat lung cells and was moderate but constant in fetal canine thymus cells. The amounts of virus released by the simian DBS-FRhL-1 and caprine S-743 cultures were low to moderate during the first 4 to 8 weeks and decreased thereafter. In the infected fetal lamb spleen cell cultures, virus production was low and declined further with passage. Bovine embryonic spleen and human diploid embryonic lung WI-38 cell cultures produced very small amounts of virus only during the first two passages after inoculation despite the fact that they remained infected, as determined by the continuous presence of cell BLV antigen and syncytia. Morphologically and antigenically, the virus particles released by the monolayer cell cultures were indistinguishable from those found in short-term and long-term cultures of BLV-infected bovine lymphoid cells. Repeated electron microscopic examinations and serological tests showed that all the BLV-infected cultures, including those from which the infecting inocula were obtained, were free of the foamy-like bovine syncytial virus, parainfluenza 3 virus, infectious bovine rhinotracheitis virus, bovine viral diarrhea virus, and the maedi-like bovine R-29 virus.

https://cancerres.aacrjournals.org/content/canres/36/11_Part_1/4152.full.pdf

In Vitro Transmission and Propagation of the Bovine Leukemia Virus in Monolayer Cell Cultures

Summary
A virus designated bovine leukaemia virus (BLV), associated with leukaemia in cattle and previously demonstrated to induce the disease in sheep, was purified from chronically infected sheep cell cultures. Electrophoretic analysis showed a major protein of mol. wt. about 24000 (p24) which reacted in gel diffusion and complement-fixation tests with sera from naturally infected cattle, experimentally infected sheep, and guinea pigs immunized with p24. BLV p24 has an isoelectric point of 8.6. Interspecies antigenic reactivities characteristic of mammalian Type C virus p30s were not detected in disrupted BLV or on p24. Sheep and guinea pig antisera to BLV, reactive withp 24, also did not precipitate several Type C virus p30s in radioimmunoassays. BLV is also distinguished from Type C viruses and resembles mouse mammary tumour virus and Mason-Pfizer virus in having an RNA-dependent DNA polymerase which is preferentially active in the presence of Mg++ when synthetic templates are used. Along with previously published morphological data, the above indicates that BLV is not a Type C virus as classically defined. Four hundred and forty one human sera from cancer patients and matched controls were non-reactive with disrupted BLV, BLV infected cells, and BLV p24 in complement-fixation tests.

M. J. Van Der Maaten

Papers

Characteristics of the major internal protein and RNA-dependent DNA polymerase of bovine leukaemia virus.