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Relationship between Moloney MSV tumor resistance and endogenous virogene expression in AKR mouse strain and its
Abstract:
We have examined the induction of Moloney-MSV tumors in AKR and other mouse strains in relation to endogenous virus expression. All virus-free strains so far tested were tumor-susceptible, while AKR was resistant. The selectivity of MSV tumor resistance, characteristic of AKR mice, was associated with AKR virogens segregation in first backcross to MuLV-negative/MSV-susceptible mice, and in a few second backcross families. Stronger evidence that AKR ecotropic virogene expression is the major, but not the sole, determinant of M-MSV tumor resistance in AKR mice was obtained in strains partially congeneic for akv-2 viral gene and in recombinant inbred lines derived from an original cross between AKR and C57L mice. These mice or lines, in which inheritance of endogenous viral genes had occurred, at the same time inherited the ability to show strong resistance to tumor induction by an exogenous oncogenic virus. This finding suggests that ecotropic endogenous viruses can exert a beneficial effect in their hosts providing some protective functions. Although the association between AKR-MuLV and M-MSV resistance is definite, the mechanisms by which MuLV+ mice are refractory to M-MSV tumors have still to be elucidated.
Insights
AKR mice exhibit resistance to Moloney-MSV tumors, linked to endogenous retroviral gene expression. This suggests a protective role for endogenous ecotropic viruses against oncogenic virus-induced tumors.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Endogenous retroviruses are integrated into host genomes and can be expressed.
- Moloney murine sarcoma virus (M-MSV) induces tumors in susceptible mouse strains.
- AKR mice are known for high endogenous ecotropic retrovirus expression.
Purpose of the Study:
- To investigate the relationship between endogenous virus expression and Moloney-MSV tumor induction in mice.
- To determine if endogenous retroviral genes influence susceptibility to M-MSV-induced tumors.
- To explore the potential protective role of endogenous viruses.
Main Methods:
- Tumor induction experiments using Moloney-MSV in various mouse strains, including AKR and congenic strains.
- Genetic analysis of endogenous retroviral gene segregation in backcross and recombinant inbred lines.
- Phenotypic assessment of tumor susceptibility and resistance.
Main Results:
- Virus-free mouse strains were susceptible to M-MSV tumors, while AKR mice were resistant.
- AKR mice resistance to M-MSV tumors was associated with endogenous ecotropic virogene expression.
- Inheritance of endogenous viral genes correlated with resistance to M-MSV tumor induction.
Conclusions:
- Endogenous ecotropic retroviral gene expression is a major determinant of resistance to Moloney-MSV tumor induction in AKR mice.
- Endogenous viruses may provide a beneficial protective function against oncogenic viruses.
- The precise mechanisms underlying this M-MSV resistance require further investigation.