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H-2-linked regulation of xenotropic murine leukemia virus expression
Abstract:
A high proportion of lymphocytes from F/St mice produce infectious xenotropic murine leukemia virus (X-MuLV) and express high levels of cell surface antigens, termed XenCSA, related to the major glycoprotein of X-MuLV. In crosses of F/St with AKR, the high-virus phenotype of F/St was found to be recessive and was shown to be governed by a single locus, Cxv-1, less than 2 centimorgans from H-2K. The close association of Cxv-1 with the H-2 complex was confirmed by the observation that B10.F mice, congeneic for the H-2 region of F/St, expressed high levels of infectious X-MuLV and XenCSA, whereas C57BL/10 mice and other C57BL/10 H-2 congeneic strains did not. Studies of hybrid mice homozygous for Cxv-1s, but segregating for a chromosome 1 X-MuLV induction locus (V locus) of F/St, demonstrated that the high-virus phenotype of F/St was dependent on the interaction between Cxv-1 and the chromosome 1 V locus.
Insights
The F/St mouse strain exhibits a high-virus phenotype, producing infectious xenotropic murine leukemia virus (X-MuLV). This trait is controlled by the Cxv-1 gene interacting with a chromosome 1 V locus, indicating a complex genetic basis for viral production.
Area of Science:
- Virology
- Immunogenetics
- Mouse Models
Background:
- F/St mice lymphocytes produce infectious xenotropic murine leukemia virus (X-MuLV).
- These cells express high levels of cell surface antigens (XenCSA) linked to X-MuLV.
- Understanding the genetic control of X-MuLV production is crucial for viral pathogenesis research.
Purpose of the Study:
- To investigate the genetic basis of the high-virus phenotype in F/St mice.
- To identify the specific genetic loci controlling X-MuLV production and XenCSA expression.
- To elucidate the interaction between different genetic factors influencing viral replication.
Main Methods:
- Genetic crosses between F/St and AKR mouse strains.
- Analysis of viral production and XenCSA expression in hybrid mice.
- Congeneic mouse strain analysis (B10.F and C57BL/10) to map genetic loci.
- Segregation analysis of chromosome 1 loci in hybrid mice.
Main Results:
- The high-virus phenotype in F/St mice is recessive and controlled by a single locus, Cxv-1.
- Cxv-1 is located less than 2 centimorgans from the H-2K region, indicating linkage to the H-2 complex.
- Congeneic B10.F mice, carrying the F/St H-2 region, showed high X-MuLV and XenCSA levels, unlike C57BL/10 mice.
- The high-virus phenotype depends on the interaction between Cxv-1 and a chromosome 1 X-MuLV induction locus (V locus).
Conclusions:
- The genetic control of X-MuLV production in F/St mice involves at least two loci: Cxv-1 near H-2K and a V locus on chromosome 1.
- The interaction between Cxv-1 and the V locus is essential for the high-virus phenotype.
- This study provides insights into the complex genetic regulation of retroviral replication in mice.