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Genetic interactions in the spontaneous production of endogenous murine leukemia virus in low leukemic mouse strains
Abstract:
The spontaneous expression of ecotropic murine leukemia virus (MuLV) in spleen cells of BALB/c, C57BL/6 (B6), and derivative mice was examined as a function of age. The patterns of spontaneous virus induction in vivo correlate with the patterns of virus induction in vitro, which result from the action of two loci, Inc-l and Inb-l (7). Whereas mice carrying Inc-l or Inb-l have similar phenotypes in vitro, they have significantly different phenotypes in vivo. Mice of the Inb-l+/+ genotype, e.g., B6, rarely expressed MuLV, and the titer of MuLV recovered from rare MuLV-positive mice of this genotype was usually low. Mice of the Inc-l+/+ genotype, e.g., BALB/c, expressed low amounts of MuLV early in life, however, from 6-12 mo of age approximately one-half of the Inc-l+/+ mice expressed virus, frequently of high titer. Equal numbers of N-tropic and B-tropic MuLV were recovered from Inb-l+ mice, but predominantly N-tropic MuLV was recovered from Inc-l+ mice. Strains that carry dominant (+) alleles at both Inc-l and Inb-l show higher titers of MuLV earlier in life than strains that carry only Inc-l or Inb-l. The presence of dominant alleles at both loci results in the appearance of predominantly N-tropic virus early in life. These results demonstrate that the principal determinants of spontaneous virus expression in these low leukemic strains of mice are the In loci or genes linked to them. A further inference that can be drawn from these studies is that the appearance of B-tropic virus is by no means a random process but rather results from predictable patterns of MuLV expression and alteration.
Insights
Spontaneous murine leukemia virus (MuLV) expression in mice is controlled by specific genetic loci. These In loci influence the timing and type of MuLV, like N-tropic and B-tropic, observed in different mouse strains.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Spontaneous expression of ecotropic murine leukemia virus (MuLV) varies across mouse strains.
- Genetic factors, specifically two loci (Inc-l and Inb-l), are known to influence MuLV induction.
- Understanding these genetic controls is crucial for studying viral pathogenesis and host responses.
Purpose of the Study:
- To investigate the age-dependent patterns of spontaneous ecotropic MuLV expression in spleen cells of different mouse strains.
- To elucidate the distinct roles of the Inc-l and Inb-l genetic loci in modulating MuLV induction in vivo and in vitro.
- To determine the tropism (N-tropic vs. B-tropic) of MuLV expressed under the influence of these loci.
Main Methods:
- Age-related analysis of spontaneous MuLV expression in spleen cells of BALB/c, C57BL/6 (B6), and derivative mouse strains.
- Comparison of in vivo and in vitro MuLV induction patterns.
- Genotyping for Inc-l and Inb-l loci to correlate with observed MuLV phenotypes.
- Quantification and characterization of MuLV titers and tropism (N-tropic and B-tropic).
Main Results:
- In vivo MuLV expression patterns correlate with in vitro induction patterns influenced by Inc-l and Inb-l loci.
- Mice with the Inb-l+/+ genotype (e.g., B6) rarely expressed MuLV, and titers were low.
- Mice with the Inc-l+/+ genotype (e.g., BALB/c) showed increased MuLV expression, often high-titered, from 6-12 months of age.
- Inb-l+ mice yielded equal numbers of N-tropic and B-tropic MuLV, while Inc-l+ mice predominantly yielded N-tropic MuLV.
- Strains with dominant alleles at both loci exhibited higher MuLV titers earlier in life, with predominantly N-tropic virus.
Conclusions:
- The Inc-l and Inb-l loci are principal determinants of spontaneous MuLV expression in low-leukemic mouse strains.
- The appearance of B-tropic MuLV is not random but follows predictable patterns of expression and alteration.
- Genetic control over MuLV expression influences viral tropism and age-dependent induction patterns.