PubMed Health⌕ Search

Biomedical subjects

H Beug

Publications and source records attributed to H Beug.

At least 181 records · Page 10Linked to original sources

Mutant avian erythroblastosis virus with restricted target cell specificity.

Avian erythroblastosis virus (AEV) induces a fatal erythroblastosis within 2 weeks of intravenous injection in chicks in virtually 100% of cases. In chicks injected intramuscularly, sarcomas frequently develop at the site of injection before the animals die from erythroblastosis. In vitro, AEV transforms both erythroblasts, derived from bone marrow cultures, and fibroblasts. These effects have been shown to be a general property of AEV and not of separate leukaemia- and sarcoma-inducing forms of the virus. AEV is defective for replication and can be propagated only in the prewence of helper virus. Its transformation specificity is independent of the helper virus used. It is not clear whether AEV has two different genes controlling transformation of the two types of target cell or whether it has only one gene coding for both. To investigate this question, we looked for mutants of AEV unable to transform one of the two types of target cell. We now describe such a mutant, which is defective for erythroblast transformation but which can still transform fibroblasts.

Alpharetrovirus↗

Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation.

The RNAs of seven replication-defective leukaemia virus (DLV) strains contain three types of unique sequences, which correlate with the capacity of a given virus strain to transform erythroblasts, macrophage-like cells and myeloblasts, respectively. These sequences, termed erb, mac and myb, have their counterparts in the normal DNA of avian and mammalian species. Our results indicate that DLVs represent recombinants between a common 'vector' related to a chicken endogenous virus and one of three types of cellular gene possibly involved in haematopoietic differentiation.

Avian Leukosis Virus↗

Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation.

Chicken hematopoietic cells transformed in vitro and in vivo by seven strains of replication-defective avian leukemia viruses were assayed for the expression of six erythroid and five myeloid differentiation parameters, including differentiation-specific surface antigens as detected by newly developed antisera. The transformed cells were found to display three distinct phenotypes of differentiation. First, cells transformed by AEV resemble erythroblasts. They express heme, globin, carbonic anhydrase and erythrocyte cell surface antigen at low levels, and histone H5 and erythroblast cell surface antigen at high levels. Second, cells transformed by MC29, CMII, OK10 and MH2 viruses have macrophage-like properties. They strongly express Fc receptors, phagocytic capacity and macrophage cell surface antigen, but only weakly express myeloblast cell surface antigen and are negative for ATPase activity. Third, cells transformed by AMV and E26 viruses resemble myeloblasts in that they weakly express Fc receptors, phagocytic capacity and macrophage cell surface antigen but strongly express myeloblast cell surface antigen and ATPase activity. No difference was found between in vitro- and in vivo-transformed cells in the parameters tested. In light of recent genetic and biochemical evidence, we believe that these phenotypes reflect the action of three new types of viral-transforming genes, designated erb (erythroblast), mac (macrophage) and myb (myeloblast).

Adenosine Triphosphatases↗

Temperature-sensitive mutant of avian erythroblastosis virus suggests a block of differentiation as mechanism of leukaemogenesis.

A temperature sensitive mutant has been isolated for the first time from a replication defective acute leukaemia virus, AEV. In vivo, at 41 degrees C, the mutant shows a reduced leukaemogenic potential. In vitro, in erythroblasts transformed at 35 degrees C, haemoglobin synthesis can be induced by a shift to 41 degrees C. This indicates that the continuous expression of a viral gene product is necessary to maintain the undifferentiated state of the virus-transformed leukaemia cells.

Alpharetrovirus↗

Differential expression of Rous Sarcoma virus-specific transformation parameters in enucleated cells.

Chicken embryo fibroblasts transformed with the Ta and ts68 mutants of Rous Sarcoma virus (RSV) were enucleated and studied for their capacity to express reversibly the transformed phenotype in response to temperature changes. After shift to the permissive temperature (35 degrees C), the cytoplasts acquired a transformed morphology and displayed characteristic ruffles and microvilli at their surface. As detected by immunofluorescence, they also lost their actin filament cables and exhibited characteristic changes in the pattern of cell surface structures containing LETS protein. Expression of all these transformation parameters was reversible after shiftback to the nonpermissive temperature (41 degrees C). These results indicate that a whole set of changes characteristic for the transformed phenotype can be expressed independently of the cell nucleus. In contrast, ts mutant-infected cytoplasts were no longer able to respond to temperature shifts with changes in their hexose transport rate. Cytoplasts prepared from cells grown at 41 degrees C retained their low rate of hexose uptake after shift to 35 degrees C, whereas cytoplasts from cells grown at 35 degrees C exhibited a high rate of hexose transport even after 10 hr of shift to 41 degrees C. These results are in accordance with the hypothesis that the product of the src gene of RSV represents a multifunctional protein which acts independently on nuclear and extranuclear sites.

Actins↗

Oncornavirus-induced sarcoma formation obscured by rapid development of lethal leukemia.

Injection i.v. of avian erythroblastosis virus (AEV) strain ES4 causes a high incidence of leukemia and the death of most of the inoculated chicks within 2 weeks. As found earlier, the virus is defective for replication and transforms bone marrow cultures in vitro, and surprisingly, also chick embryo fibroblasts. Inoculation of transformed AEV cells negative for virus production into newborn chicks induced the formation of sarcomas only, whereas cells superinfected with helper virus induced the formation of erythroblastosis in addition to sarcomas. The helper virus alone caused neither sarcomas nor erythroblastosis during the experimental period. These findings were explained by the hypothesis that AEV-induced erythroblastosis develops more rapidly than do AEV-induced sarcomas and that animals receiving i.v. injections die of the leukemia before sarcomas become detectable. The observation that animals receiving i.m. injections of AEV developed sarcomas at the site of injection strongly supports this concept. Most of the animals that received i.m. injections also developed an erythroblastosis that was delayed, however, in comparison to the animals receiving i.v. injections. Our data also suggest that the erythroblastosis induced by AEV does not suppress the formation of sarcomas in the same animal.

Alpharetrovirus↗