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Published on: May 27, 2011
Suppression of Moloney sarcoma virus immunity following sensitization with attenuated virus
Abstract:
Murine sarcoma virus (Moloney strain) (MSV-M)-induced tumors are unusual in that they regularly appear less than 2 weeks after virus inoculation, progress for 1 to 2 weeks, and are rejected by normal adult BALB/c mice. Rejectio leaves the animals immune to tumor induction. In the present study, presensitization of normal adult BALB/c mice with attenuated MSV-M resulted in an altered pattern of tumor immunity. Injection of active MSV-M into the presensitized animals resulted in tumor induction and rejection similar to that observed in normal animals, but rejection failed to produce protection against the secondary inoculation with MSV-M. After the second inoculation with active MSV-M, tumors appeared and progressed but ultimately were rejected. Over 80% of the mice died, 25% after the primary challenge and the remainder after the secondary challenge. At death, all mice had histological evidence of leukemia which was the probable cause of death. The animals that died following the secondary challenge also had evidence of disseminated MSV-M. Solid tumor nodules were found in skeletal muscle distant from the original site of inoculation, and active MSV-M was isolated from spleen and lungs. The possibility that the results were produced by specific suppression of MSV-Moloney leukemia virus immunity is discussed.
Insights
Presensitizing mice with Moloney murine sarcoma virus (MSV-M) altered tumor immunity. While initial tumors were rejected, subsequent challenges led to leukemia and death, suggesting immune suppression.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Murine sarcoma virus (Moloney strain) (MSV-M) induces tumors that are typically rejected by adult BALB/c mice, conferring immunity.
- Tumor rejection usually results in long-term protection against subsequent viral challenges.
Purpose of the Study:
- To investigate the impact of presensitization with attenuated MSV-M on the immune response to active MSV-M challenge.
- To determine if presensitization alters the protective immunity typically observed after tumor rejection.
Main Methods:
- BALB/c mice were presensitized with an attenuated strain of MSV-M.
- Presensitized mice were subsequently challenged with active MSV-M.
- Tumor development, rejection dynamics, and survival rates were monitored.
- Histological analysis and viral isolation were performed on deceased animals.
Main Results:
- Presensitization led to initial tumor induction and rejection, similar to normal mice.
- However, rejection after the primary challenge failed to confer protection against a secondary MSV-M inoculation.
- Over 80% of presensitized mice died, primarily from leukemia, with evidence of disseminated MSV-M in those succumbing after secondary challenge.
Conclusions:
- Presensitization with attenuated MSV-M can paradoxically impair protective immunity against subsequent challenges.
- The observed mortality suggests a potential for immune suppression or altered immune regulation in response to MSV-M.
- Leukemia is a significant cause of mortality in this model, particularly after secondary viral challenge.
