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Host control of endogenous murine leukemia virus gene expression: concentrations of viral proteins in high and low
Abstract:
Two of the major molecular components of murine leukemia virus particles, the internal protein (p30) and the envelope glycoprotein (gp69/71) have been measured in the spleens of normal, 6- to 10-week-old mice of various inbred strains and crosses. Both proteins were detected in virtually all mice. Extracts of high leukemia, high murine leukemia virus strains (AKR, C58, PL) showed high levels of both proteins; extracts of other strains usually showed lower levels. Of particular interest, however, were the exceptions to these general observations: (1) Very little gp69/71 could be detected in spleens of BALB mice, and this trait was dominant in crosses with AKR and DBA/2, both of which express a high level of gp69/71. Thymus-deficient BALB/c-nu/nu (nude) mice, in contrast, showed a higher concentration of gp69/71 typical of other low leukemia strains, suggesting that the virtual absence of the protein in normal BALB/c mice may result from immunologic suppression. (2) With C57L, C57BL/10Sn, and C57BL/6 strains the concentration of p30 was lower, in some cases much lower, than would be expected from the concentration of gp69/71. (3) DBA/2 mice showed high levels of gp69/71, 10-fold greater than that of p30, whereas congenic DBA/2-Fv-1(b) mice showed the opposite pattern. (4) Mice of 129-G(IX) (-) strain showed no detectable levels of either p30 or gp69/71 proteins, although the congenic 129 (G(IX) (+)) showed appreciable levels of both. The absence of these proteins in 129-G(IX) (-) mice is a recessive trait, as F(1) hybrids with AKR and DBA/2 showed appropriate levels of both proteins. It is concluded that expression of viral p30 and gp69/71 proteins in mice is not coordinately linked and that expression is complex, being influenced by several genes, including Gv-1, H-2, Fv-1, and probably still others.
Insights
Murine leukemia virus proteins p30 and gp69/71 expression varies significantly across mouse strains, influenced by multiple genes. This suggests complex, non-coordinate regulation of viral protein production in mice.
Area of Science:
- Virology
- Immunogenetics
- Molecular Biology
Background:
- Murine leukemia viruses (MLVs) are retroviruses associated with leukemia in mice.
- Key viral components include the internal protein p30 and envelope glycoprotein gp69/71.
- Understanding the genetic control of MLV protein expression is crucial for leukemia research.
Purpose of the Study:
- To quantify levels of MLV p30 and gp69/71 proteins in spleens of various inbred mouse strains and crosses.
- To investigate the genetic basis for variations in MLV protein expression.
- To determine if p30 and gp69/71 expression are coordinately regulated.
Main Methods:
- Measurement of p30 and gp69/71 protein concentrations in spleen extracts using immunological assays.
- Analysis of protein levels in different inbred mouse strains and their F1 hybrids.
- Correlating protein levels with known genetic markers and disease phenotypes.
Main Results:
- Both p30 and gp69/71 proteins were detected in most mice, with higher levels in high-leukemia strains.
- Significant exceptions were observed, such as low gp69/71 in BALB mice (potentially due to immune suppression) and variable p30 levels.
- Specific mouse strains (e.g., 129-G(IX)(-)) showed absence of both proteins, indicating recessive genetic control.
- DBA/2 and congenic DBA/2-Fv-1(b) mice exhibited distinct p30/gp69/71 ratios, highlighting strain-specific regulation.
Conclusions:
- Expression of MLV p30 and gp69/71 proteins is not coordinately linked.
- Viral protein expression is a complex trait influenced by multiple host genes, including Gv-1, H-2, and Fv-1.
- These findings provide insights into the genetic control of retroviral susceptibility and pathogenesis in mice.