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Structure and expression of endogenous ecotropic murine leukemia viruses in RF/J mice
Abstract:
High leukemic mouse strains possess proviral genomes that are more inducible for virus expression by halogenated pyrimidines than the proviral genomes harbored by low leukemic mice. We investigated the induction and arrangement of ecotropic proviruses in RF mice, a strain of mouse that develops a moderate incidence of leukemia late in life. We found that RF mice, unlike either high or low leukemic inbred strains, carried both a gene for high efficiency virus induction (Rjv-1) and a gene for low efficiency virus induction (Rjv-2). Virus induction from mice that contained Rjf-2 alone was observed only in crosses with two other strains that carried ecotropic proviruses, i.e., DBA/2 and C57BL/6, and not in crosses performed with mice that lacked ecotropic proviruses, i.e., 129, SWR, and NFS. Inheritance of the Rjv-1 gene frequently resulted in viremia when a virus-suppressive gene(s) of RF (most likely Fv-1) was not present in the same individual. Rjv-1 and Rjv-2 virus induction genes co-segregated with ecotropic proviruses integrated in different cellular DNA sequences. Rjv-2, the less inducible ecotropic provirus in RF mice, is located in cellular DNA sequences very similar to those found adjacent to the ecotropic provirus of BALB/c. These results document a second system of virus interaction or complementation and demonstrate that ecotropic proviruses of different phenotypes can be found within an individual mouse strain.
Insights
RF mice possess unique genes for high (Rjv-1) and low (Rjv-2) efficiency virus induction. These genes influence ecotropic provirus expression and complementation, differing from high and low leukemic mouse strains.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- High leukemic mouse strains show greater proviral genome inducibility for virus expression.
- Ecotropic proviruses are endogenous retroviral sequences found in mouse genomes.
- Leukemia development in mice is influenced by genetic factors and viral induction.
Purpose of the Study:
- To investigate the induction and arrangement of ecotropic proviruses in RF mice, a strain with moderate leukemia incidence.
- To characterize the genetic basis of virus induction in RF mice and compare it to high and low leukemic strains.
Main Methods:
- Cross-breeding RF mice with other inbred strains (DBA/2, C57BL/6, 129, SWR, NFS) to study inheritance patterns.
- Analyzing virus induction efficiency and viremia in offspring.
- Investigating the co-segregation of virus induction genes (Rjv-1, Rjv-2) with ecotropic proviruses.
Main Results:
- RF mice possess both high (Rjv-1) and low (Rjv-2) efficiency virus induction genes.
- Rjv-2 induction required co-existing ecotropic proviruses from other strains.
- Rjv-1 inheritance led to viremia in the absence of virus-suppressive genes (e.g., Fv-1).
- Rjv-1 and Rjv-2 genes were linked to ecotropic proviruses in distinct DNA sequences.
- Rjv-2 provirus location is similar to that in BALB/c mice.
Conclusions:
- RF mice exhibit a unique dual system for ecotropic provirus induction and complementation.
- Different phenotypes of ecotropic proviruses can exist within a single mouse strain.
- Genetic factors significantly influence viral induction and potential leukemogenesis.