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Biomedical subjects

M Mammerickx

Publications and source records attributed to M Mammerickx.

At least 73 records · Page 4Linked to original sources

Genomic integration of bovine leukemia provirus: comparison of persistent lymphocytosis with lymph node tumor form of enzootic.

Integration of bovine leukemia proviral DNA in the genome of infected cells was investigated in cattle affected by either the persistent lymphocytosis or the lymph node tumor form of enzootic bovine leukosis. In persistent lymphocytosis, proviral DNA was found to be integrated at a large number of genomic sites in one-fourth to one-third of circulating leukocytes. In the lymph node tumor form, in contrast, proviral DNA was found to be integrated at one or very few sites in the genomes of a larger fraction of both circulating leukocytes and lymph node tumor cells.

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BLV proviral DNA in the genome of the target lymphocyte.

Integration of bovine leukemia proviral DNA in the genome of infected cells was investigated in cattle affected by either the persistent lymphocytosis or the lymph node tumor form of enzootic bovine leukosis. In persistent lymphocytosis, proviral DNA was found to be integrated at a large number of genomic sites in one-fourth to one-third of circulating leucocytes. In the lymph node tumor form, in contrast, proviral DNA was found to be integrated at one or very few sites in the genomes of a larger fraction of both circulating leucocytes and lymph node tumor cells.

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Integration of bovine leukemia virus DNA in the bovine genome.

DNA preparations from circulating leukocytes, lymph node tumors, and spleens of three bovine leukemia virus-infected cattle were fractionated by Cs2SO4/3,6-bis(acetatomercurimethyl)dioxane density gradient centrifugation. Bovine leukemia virus proviral sequences were found in large GC-rich fragments having a buoyant density in CsCl close to 1.708 g/cm3. Provirus integration, therefore, does not take place at random locations in the host genome, but in a specific class of DNA segments. Hybridization of cDNA synthesized on viral RNA to EcoRI and Xba I restriction fragments of the DNA from infected cells showed that: (i) only one copy of proviral DNA is integrated per haploid genome; (ii) different restriction patterns were found in the proviral DNAs present in the genomes of different animals, providing evidence for the existence of several strains or mutants; and (iii) different integration sites for the proviral DNA were found in the genome of different animals and of different infected cells in the same animal. The latter finding strongly suggests a polyclonal origin of bovine leukemia virus-infected cells.

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Humoral antibody response to bovine leukemia virus infection in cattle and sheep.

In this study, 345 cattle from 7 herds with a history of lymphosarcoma were tested for antibody to BLV antigens by three serological methods, namely immunodiffusion using a bovine leukemia virus glycoprotein with a molecular weight of 60,000 as antigen, and radioimmunoassay using a bovine leukemia virus glycoprotein with a molecular weight of 60,000 and a bovine leukemia virus protein with a molecular weight of 24,000 as antigen. The three tests under comparison agreed for 335 animals, 240 being negative in the three tests, and 95 being positive. Results were variable in ten cases only. Glycoprotein with a molecular weight of 60,000 antibody titers were systematically higher than were protein with a molecular weight of 24,000 antibody titers in bovine sera and milk, as well as in sera of experimentally infected sheep. In the latter case, antibodies to bovine leukemia virus antigens reached maximal values at the animal death in the tumor phase of the disease. Ratios of serum antiglycoprotein titer to milk titer varied between 4 and 117, showing that, if milk pools are to be used in surveys of bovine leukemia virus infection, use of very sensitive techniques of detection is mandatory.

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Detection of complement-dependent lytic antibodies in sera from bovine leukemia virus-infected animals.

Cattle and sheep infected by Bovine Leukemia Virus (BLV) harbor complement-dependent cytotoxic IgG1 antibodies. These antibodies lyse BLV producing cells but are inactive against noncultured tumorous lymphocytes of animals with persistent lymphocytosis. The target structure in the cell membrane contains antigenic determinants of BLV gp 60. The level of cytotoxic activity increases with progression of the disease towards the tumor phase. Sheep vaccinated with inactivated BLV have no cytotoxic activity in the serum but seem to resist infectious BLV challenge. Such cytotoxic activities do not protect the host against tumor growth but strongly control viremia and thus limit BLV spread within bovine and ovine populations.

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Distribution of bovine leukemia virus proviral sequences in tissues of bovine, ovine and human origin.

Bovine leukemia virus (BLV) single-stranded cDNA was used to study the distribution of DNA sequences in tissues (normal or malignant) from bovine, ovine and human origin. After recycling against normal bovine DNA, BLV (3H) cDNA hybridized with bovine enzootic tumor DNA but did not hybridize with normal bovine DNA. These results indicate that BLV is an exogenous RNA oncogenic virus and confirm that enzootic bovine leukosis (EBL) is an infectious disease. Proviral BLV sequences were also detected in buffy coat cells of animals in persistent lymphocytosis (PL) and carrying antibodies to BLV but no tumors. In animals at the tumor stage of EBL, the proviral sequences were found in buffy coat cells, in solid tumors (lymphosarcomas) and in organs infiltrated with tumoral lymphoid cells but not in apparently normal organs. No hybridization above background was observed between BLV (3H) cDNA and DNAs extracted from buffy coat cells and tumors corresponding to sporadic forms of bovine leukosis and some human leukemias and sarcomas.

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