H.-J. Thiel

Properties of mouse leukemia viruses. Xiii. Serum therapy of virus-induced murine leukemias.

Abstract Treatment of STU mice with antiserum to the major glycoprotein (gp71) of Friend leukemia virus (FLV) was therapeutically active against massive infection with Friend or Rauscher viruses, whereas similar treatment with antisera to p12 and p15, two other proteins of the virion which are involved in surface reactions, were not effective. A more thorough study showed that the active principle is contained in the IgG fraction of gp71 antiserum and that treatment with this can lead to complete recovery of the mouse from FLV infection. As a consequence of the treatment, the host produces type-specific antibodies which are detectable by neutralization, radioimmunoassay with FLV gp71, and cytotoxic tests on FLV-infected cells. No significant change was observed in the pattern of autogenous antibodies directed against an AKR-type gp71 already present in normal mice. Treatment with immune serum instead of immune IgG or treatment with immune IgG at a later stage of infection with FLV (after 7 days p.i.) did not result in complete recovery of the mice. Paralysis of the host immune system by serum proteins and Friend virus, respectively, seems to be responsible for these phenomena. Some indication was obtained that the viral-induced paralysis can be overcome by combined inoculation of heterologous immune IgG and normal isogenic spleen and bone marrow cells.

Properties of mouse leukemia viruses. XIV. Prevention of spontaneous AKR leukemia by treatment with group-specific antibody against the major virus gp71 glycoprotein.

Treatment of AKR mice early in life with potent goat antibody to the major virus glycoprotein (gp71) of Friend leukemia virus resulted in marked prevention of fatal AKR disease. Even better protection could be achieved when, in addition, the mothers were treated with the same antibody at least 3-4 days antepartum. From these preliminary observations, we conclude that antibody specific for the broadly cross-reacting determinants of this virus glycoprotein can control development of spontaneous leukemias mediated by replicating endogenous viruses.

Studies of Simian Sarcoma and Simian Sarcoma-Associated Virus: I. Analysis of Viral Structural Proteins, and Preparation and Characterization of Antiserum Specific for Viral Envelope Components

The structural proteins of simian sarcoma virus type 1 and its associated virus (SSV) were analysed; in general they were similar to the corresponding components of murine leukemia viruses (MuLV), i. e. glycoproteins of approximately 69.000 and 71.000 Daltons (gp69/71), proteins corresponding to p15(E) and p12(E) which were identified as envelope, and p31, p15, p12 and p10 proteins identified as internal components. As in MuLV, p12 stained reddish with Coomassie blue but a pl5(C) distinct from p15(E) was not clearly identified. Using antisera specific for individual components of MuLV cross-reactions were observed between the proteins pl5(E), pi2(E) and p31 of SSV and MuLV, and to a minor degree also between their respective major glycoproteins. An antiserum reacting strongly, specifically and almost exclusively with the envelope components of SSV gp69/71, p15 (E) and p12 (E) was prepared in a goat by inoculation of the animal’s own cells, previously transformed in vitro with SSV and grown in goat serum. Comparative studies with this antiserum in complement fixation and Ouchterlony tests confirmed the strong antigenic similarities between SSV and gibbon ape lymphoma virus but did not identify any interspecies reactivity.

Studies of simian sarcoma and simian sarcoma-associated virus II. Isolation of the major viral glycoprotein, properties of this component and its specific antiserum

Abstract Using immunoadsorbents, the major glycoprotein gp70 of the simian sarcoma virus complex (SSV) was isolated in highly pure form and preparative amounts from virus-free supernatants of tissue culture medium. The SSV gp70 possesses type, group, and interspecies antigenicity but has no demonstrable interfering activity. Antiserum prepared in rabbits to the purified SSV gp70 has a high neutralizing titer against SSV and is strongly cytotoxic for SSV-producing cells. Various serological tests indicate that the serum reacted preferentially with type-specific determinant(s) of the viral glycoprotein. Gp70 degraded easily to smaller components, preferentially to gp45. Serologically, isolated gp45 was similar to gp70, but showed a decrease in interspecies antigenicity.

Properties of mouse leukemia viruses XVII. Factors required for successful treatment of spontaneous AKR leukemia by antibodies against gp71

Abstract AKR mice were treated with heterologous anti-gp71 antibodies under various conditions in order to establish the optimal criteria for effective suppression of leukemia development. The strongest effect was observed when mice were treated at birth; and when this regimen was used, prior treatment of the mothers did not provide additional protection. If treatment was delayed until Day 3 ( Schwarz et al. , 1979 ), the beneficial effect of the serum diminished sharply, emphasizing the presence of a narrow window very early in the life of the AKR mouse when antibody must be present in order to have an effect on subsequent leukemia development. A number of parameters were examined in the experimental mice and as in our previous study ( Schwarz et al. , 1979 ), suppression of leukemia, which occurred in 68% of the animals, correlated with elimination of viremia and appearance of natural antiviral antibodies. Interestingly, our results suggest that antibody therapy is primarily effective against the thymic form of the disease. The availability of nonviremic, antibody-positive animals afforded us the opporounity to examine if these characteristics could be transmitted to the offspring. From selected mating crosses, we successfully derived both F1 and F2 generations of AKR mice which possessed high titers of antiviral antibodies and were nonviremic at 21–28 weeks of age. It appeared that a maternal effect may be responsible for this phenomenon. The implications of these findings are discussed in relation to the development of AKR leukemogenesis.

Interspecies reactivity of type C and D retrovirus p15E and p15C proteins

Abstract Two low-molecular-weight structural components of mammalian type C viruses p15E and p15C were studied in terms of their content of interspecies antigenic reactivity. We find that both components possess broadly cross-reacting determinants, which in the case of p15E extend to primate type D viruses.

Immuno-Prophylaxis and -Therapy of C-Type Oncorna Viral Diseases in Mice and Cats

1Max-Planck-lnstitut fiir Virusforschung, D-7400 Tiibingen, Federal Republic of Germany 2Duke University, Dept. of Surgery, Durham, N.C., USA 3Cornell University, Dept. of Pathology, Ithaca, N.Y., USA 4National Cancer Institute, NIH, Bethesda, Md., USA 5Forschergruppe Tumorimmunologie, D-7800 Freiburg (Breisgau), Federal Republic of Germany 6Frederick Cancer Research Center, Frederick, Md. 21701, USA 7Institut fdr Virologie, Tieriirztl. Hochschule, D-3000 Hannover, Federal Republic of Germany

Isolation of the Major Glycoprotein (gp70) of Simian Sarcoma Virus (SSV-1/SSAV-1) in Preparative Quantities

Abstract The major glycoprotein (gp70) of simian sarcoma virus is present in “soluble” form in the medium of virus-producing suspension cultures. It could be isolated from the supernatant of such cultures in substantial amounts by an immuno-adsorbent technique. Some of its gel-electrophoretic and serological properties are described.

Properties of mouse leukemia viruses: XX. Variation of AKR substrains in response to antibody therapy

In previous reports in this series, we have demonstrated that treatment of young AKR mice with IgG prepared against the viral envelope glycoprotein suppresses the development of spontaneous leukemia. Moreover, animals exhibiting high anti-viral antibody titers can transfer protection to their offspring. In this report we have extended the studies to another strain of AKR mice and find that the ability to transfer protection to offspring was not obtained. Foster nursing experiments were therefore conducted and their outcomes are indicative that maternal factors may be responsible for this phenomenon.

Stimulierung der Immunreaktivität gegen endogene Retroviren und Schutz gegen Leukämie bei älteren AKR-Mäusen nach Impfung mit Antikörpern gegen Virusoberflächen-Komponenten. Rolle des Antikörpers gegen p15(E) / Stimulation of Immunoreactivity against Endogenous Retroviruses and Protection against Leukem ia of Older AKR Mice by Treatment with Antibodies against Retroviral Surface Components. Role of p15 (E) Antibody

Abstract Antibody against viral gp71 is effective therapeutically for high leukemic AKR mice if injected immediately after birth [1], No corresponding effect could be observed after inoculation later in life when the endogenous virus burden is already high. However, if antibody treatment was supplemented by the injection of pi5(E) antibody, a therapeutic effect was observed even in older mice first treated at an age of 21/2 months. Those mice produced antibodies against viral surface proteins and appeared to be able to survive longer than control mice. Thus pi5(E) antibody might be able to overcome retroviral associated immunodeficiency. This therapy may have implications for the treatment of the apparently retroviral induced aquired immunodeficiency syndrome (AIDS) of man.