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Biomedical subjects

M Mussgay

Publications and source records attributed to M Mussgay.

At least 19 recordsLinked to original sources

Antibodies against a preselected peptide recognize and neutralize foot and mouth disease virus.

A major antibody combining site on foot and mouth disease virus (FMDV) serotype O1K has been identified in a predicted surface helix of viral protein 1 (VP1) between amino acid residues 144 and 159. A hexadecapeptide covering this sequence elicits high titers of antibodies that specifically recognize and neutralize FMDV. The high quality of the immune response is attributed to a particularly stable conformation of the antigenic amino acid sequence, which is most likely an alpha-helix.

Amino Acid Sequence↗

Tumors induced by progressor sarcoma virus (Moloney) in mice: growth in the presence of an immune response and isolation of autonomously growing cells.

Courses of tumors, which had been induced in adult STU mice with a regressor and with a progressor strain of Moloney sarcoma virus (MSV-M) were followed and compared. All 73 tumors induced by the regressor strain of MSV-M (R-MSV-M) regressed and 181 of 183 tumors induced by a progressor strain (P-MSV-M) grew progressively and killed their hosts between 16 and 171 days after infection. Even after inoculation of about 4 FFU of P-MSV-M tumor development may occur and lead to progressively growing tumors. Both strains of MSV-M induce strong immune responses in their host, namely cytotoxic effector cells, cytotoxic antibodies and tumor resistance. Simultaneous injection of mice on separate sites with P-MSV-M on one side and R-MSV-M producing ascitic cells on the other side did not induce mutual influences on the different tumor courses. It is therefore concluded that the immune response is obviously not decisive for the failure of P-MSV-M induced tumors to regress. From seven P-MSV-M induced primary tumors two producer and five nonproducer transformants could be isolated, maintained in culture and partly held as easily transplantable tumors in adult immunocompetent mice. Both producer transformants release sarcoma virus with the capacity to induce progressively growing tumors in adult mice. All transformants induce progressively growing tumors after transplantation independent of the applied cell dose. It is concluded that the ability of the P-MSV-M to induce stably transformed cells (in contrast to R-MSV-M, WEILAND et al., Brit. J. Cancer, 1979) favours clonal development and ultimately progressive tumor course, in spite of the presence of an immune response.

Animals↗

A non-virion surface antigen on Moloney sarcoma virus-transformed non-producer and producer cells.

Sera from STU mice bearing sarcomas induced by cells producing the Moloney sarcoma-helper-virus (M-MSV/MLV) complex were cytotoxic for these cells as well as for M-MSV non-producer and M-MLV producer cells. Analysis by polyacrylamide gel electrophoresis of 125I-labelled surface antigens immunoprecipitated with such sera revealed the virus envelope glycoprotein gp71 on the producer cells and an additional antigen of mol. wt 55 K on the M-MSV-transformed producer and non-producer cells. This antigen was not found on non-transformed M-MLV-producing cells and was neither related serologically to structural polypeptides of murine C-type viruses nor to components of embryonal STU mouse fibroblasts and foetal bovine serum.

Animals↗

Growth pattern of tumours in mice induced by murine Moloney sarcoma-virus and sarcoma-virus-transformed cells.

Transplantation of a Moloney sarcoma-virus (MSV-M)-transformed producer cell line (Sac(+)) induced progressively or regressively growing tumours in mice. Progressive growth always occurred after transplantation of an MSV-M non-producer transformant (Sac(-)), whereas the MSV-M released from the producer cells (Sac virus) always induced tumours which regressed. In contrast to the non-producer, the producer transformant Sac(+) as well as Sac virus induced a strong immune response, detected in vitro by cell- and antibody-mediated cytotoxicity assays, and in vivo by transplantation immunity. Implantation of Sac(-) cells led to solid, under-vascularized tumours, consisting histologically of uniform densely packed tumour cells. Sac-virus-induced tumours, however, were very well vascularized and arose by proliferation of different connective-tissue cells. After transplantation of Sac(+) cells, tumours were found to consist of typical tumour cells morphologically similar to Sac(-) cells intermingled with proliferated connective-tissue cells. Cultivation of tumour fragments from Sac(+) and Sac(-) tumours was followed by outgrowth of transformed tumour cells with the properties of the originally implanted cells. Tumour explant cultures from Sac-virus-induced tumours did not lead to growth of stably transformed cells. Co-culture of mouse embryo fibroblasts (MEF) with Sac(+) cells resulted in overgrowth of the transformed cells. Infection of MEF with Sac virus led to transiently transformed cells. It is concluded that Sac(+) cell tumours will resist the strong immune defence mechanisms they induce and grow progressively, if the inoculated cells are able to build up a solid, poorly vascularized nodule in the tissue. This always happens after implantation of 10(6) cells, but only occasionally when fewer cells are inoculated. Sac-virus-induced tumours will always regress owing to the strong immune response. The regression is furthered by the fact that MSV-M infection rarely if ever leads to a stable transformation.

Animals↗

Nonproducer malignant tumor cells with rescuable sarcoma virus genome isolated from a recurrent Moloney sarcoma.

Cells from a secondary tumor developing at the site of a regressed Moloney sarcoma virus-induced tumor could be passaged in adult STU mice by intramuscular and intraperitoneal inoculation. The tumors induced by these cells, as well as by a cell line derived from it, grew progressively and led to death of the animals between 3 and 7 wk after tumor transplantation. No evidence for production of virus from these cells was obtained or for the presence of viral antigens (p30, gp69/71). From both cell variants, sarcoma virus genome could be rescued by infection with helper virus, resulting in the establishment of a cell line producing focus- and XC plaque-forming virus. The rescued producer cells very frequently also produced tumors which finally grew progressively. The nonproducer cells were not immunogenic, as was demonstrated in cross transplantation tests and in studies for cell-mediated cytotoxicity (CMC) and complement-dependent antibody-mediated cytotoxicity (AMC). The producer cells, however, were demonstrated to possess a strong immunogenicity. The nonproducer cells, though nonimmunogenic, revealed a weak immunosensitivity when used for challenge in the transplantation protection assay or as target cell for the demonstration of AMC and CMC, if the immune response was induced by cells producing the sarcoma-helper virus complex, but not by cells producing only helper virus. The nonproducer cells, as well as their rescued producer derivative, showed a stronger reactivity with cytotoxic antibodies than with cytotoxic cells, whereas the helper virus-producing cell line was comparably suitable as target cell for AMC and CMC. The recurrence of a regressed Moloney sarcoma is assumed to be the result of the occurrence of transformed nonproducer cells escaping immune destruction, and not as a consequence of a depleted immune resistance in the host.

Animals↗

Togaviridae.

The family Togaviridae is described; it contains four genera--Alphavirus, Flavivirus, Pestivirus and Rubivirus--and additional members. The main characteristics of the family are as follows: single-stranded, linear RNA, molecular weight about 4 X 10(6). Virions have isometric nucleocapsids surrounded by a lipoprotein envelope containing host cell lipid and virus-specified polypeptides including one or more glycopeptides. Virions yield infectious RNA. There are at least 80 members; all the alphaviruses and most flaviviruses are arboviruses in the biological sense.

Arboviruses↗

Detection of cytotoxic lymphoid spleen cells from STU-mice with Moloney sarcoma by a 3H-proline microcytotoxicity assay.

A microcytoxicity assay with 3H-proline prelabeled target cells was used for the detection of sensitized lymphoid spleen cells from STU inbred mice inoculated with Moloney sarcoma virus (MSV-M) or ascitic MSV-M tumor cells. The target cell line was derived from ascitic MSV-M tumor cells. With regard to the specificity of the assay nonimmune slpeen cells displayed no or only a weak cytotoxicity against these cells, and this was also the case when 3H-proline-labeled secondary cultures of syngeneic mouse embryo cells were exposed to both sensitized and nonimmune spleen cells. The time-course pattern of the development of cytotoxic lymphoid spleen cells in STU mice inoculated intramuscularly either with MSV-M or ascitic MSV-M tumor cells was studied. At the stages of tumor development, peak tumor size, and tumor regression the lymphoid spleen cell preparations were found to have relatively strong cytotoxic activity independent of whether the tumor was induced by MSV-M inoculation or tumor cell transplantation. However, in the latter case effector cells appeared earlier and were demonstrable for a longer period than in MSV-M-inoculated mice. Anti-theta serum treatment of lymphoid spleen cells taken at the stage of peak tumor size abrogated the cytotoxic activity or diminished it considerably indicating a T-lymphocyte response.

Animals↗