Biomedical subjects
Publications and source records attributed to N A Wivel.
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Interferon treatment of JLSV-6 cells chronically infected with Rauscher MuLV leads to the formation of noninfectious particles (interferon virions) containing the structural proteins of env and gag genes as well as additional viral polypeptides. In the control virions the major glycoprotein detected is gp71, interferon virions contain in addition to gp71 and 85k dalton (gp85) glucosamine-containing, fucose-deficient glycoprotein which is recognized by antiserum to MuLV but not by the gp71 antiserum. The surface iodination of the intact virions indicates that both gp71 and gp85 are the major components of the external virions envelope. However, unlike the control virions in which gp71 associates with p15E (gp90), the gp71-p15E complex was not detected in interferon virions. The analysis of the iodinated proteins of the disrupted interferon virions revealed the presence of 85k and 65k dalton polypeptides preciptable with antiserum against MuLV, which are not present in the control virions. The difference in the polypeptide pattern of virions produced in the presence of interferon does not seem to be a consequence of the slowdown in the synthesis of viral proteins or their processing in the interferon-treated cells. Both the structural proteins of env and gag genes seem to be synthesized and processed at a comparable rate in the interferon-treated and -untreated cells. These results indicate an alteration of virus assembly in the presence of interferon.
Interferon (150 units/ml) was used to treat SC-1 and AKR-2B cells which were chronically infected with murine leukaemia virus (MuLV). This led to a 100-fold decrease in the amount of infectious virus released into the medium and a 10-fold decrease in the number of virus particles measured by the virion-associated reverse transcriptase assay. However, there was little change in the amount of cell-associated infectious virus, though nearly twice as many cell-associated virions were counted in electron micrographs. With both types of cells, interferon blocked MuLV replication at the post-budding stage, but it did not change the morphology of the particles produced or their content of virion 70S RNA. Infectious virus assembled on the cell membranes of interferon-treated cells was less stable at 37 degrees C than that grown in the absence of interferon. Release of infectious virus from interferon-treated cells was not inhibited by actinomycin D or cycloheximide, though both agents inhibited virus production in controls. These results show that interferon inhibits MuLV replication through effects on virion assembly; these lead both to the formation of non-infectious particles and of fewer virions. Kinetic analysis further shows that interferon affects MuLV assembly rapidly and induction of an antiviral protein may not be required.
A brief review of the origin and tumor-inducing properties of Abelson murine leukemia virus is given. The most common neoplasm induced by this virus in vivo is a nonthymic lymphocytic tumor of bone marrow and lymph node origin. Two morphologic types of lymphosarcomas are the undifferentiated lymphosarcoma (LS) and the plasmacytic lymphosarcoma (PL). With the electron microscope, both tumor cell types may be mixed and contain undifferentiated cells or cells with a moderate amount of rough endoplasmic reticulum and polysomes. PL tumors are composed predominantly of the latter. In biosynthetic studies, PL tumors produce more immunoglobulin (Ig) than LS and more of the Ig-heavy chain, which is thought to be the murine counterpart of IgD. PL-cells sensitized with rabbit antisera to mouse kappa chains formed rosettes with formalinized protein-A producing Staphylococcus aureus Cowan I strain. The rabbit antisera were specific for kappa chains by absorption. The failure of lymphosarcoma cells to secrete Ig indicates their differentiation is blocked by the transformation process. Lymphosarcoma cells appear then to be derived from B-lymphocytes.
The nascent DNA transcript of intracisternal A particle RNA-directed DNA polymerase appeared to be covalently linked to an RNA primer. Fidelity of transcription is evident since the DNA transcript hybridized specifically back to 35-70 S RNA of intracisternal A particles but not with heterologous RNAs. This DNA transcript has an approximate molecular weight of 145 000, estimating 350 polynucleotides and base ratios with an excess of dGMP.
Three tissue culture clones of neuroblastoma cells derived from the C-1300 tumor in strain A/J mice were found to contain type-C virus-specific gas antigen. None of the clones spontaneously released mouse-tropic type-C viruses although one clone, N-4, spontaneously released a xenotropic virus. Two clones, NB-2A and N-4, could be induced by treatment with 5-iododeoxyuridine and dexamethasone phosphate to produce B-tropic type-C virus, but clone N-18 failed to release either ecotropic or xenotropic virus under several different induction conditions. Karyotype analysis did not reveal specific chromosome deletions in clone N-18.
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Murine intracisternal A particles have a number of properties which are common to known RNA tumor viruses, but horizontal transmission has not been previously demonstrated. The apparent absence of infectivity may be related to the failure of these particles to be released from cisternae of endo-plasmic reticulum. Previous biological studies using isolated, purified A particles have been compromised by the fact that the isolation procedure requires small amounts of nonionic detergent. Using some techniques of somatic cell hybridization, we have assessed the capacity for A particle genome transfer from positive to negative cells. Since it has been previously shown that some chloramphenicol-resistant cell lines can transfer this resistance in the cytoplasm, we have used this characteristic as a marker for cytoplasmic fragments. Mouse cells containing A particles were mutagenized, and clones resistant to chloramphenicol were selected; by enucleating these cells and fusing the resultant cytoplasts to each of two recipient mouse cell lines negative for A particles, it is possible to identify clones of cells known to be the product of a fusion event between a cytoplast and a whole cell (cybrids). Under these conditions, intracisternal A particles appear in the cybrid clones as a phenotypic trait that has not been segregated over at least 60-80 cell generations.
Intracytoplasmic A particles and intracisternal A particles are associated with mouse tumors of various types, and both can coexist in the cytoplasm of the same cell. The designation of both as A particles is based on the recognition that they share morphological similarities. A comparison of purified isolates of these two particles reveals that the structural protein profiles are different, but that there is some antigenic cross-reaction as demonstrated by immunodiffusion and complement fixation. This result does not appear to involve the major structural protein of intracisternal A particles, but may reflect the presence of common antigenic determinants located on minor proteins.
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