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Receptor-mediated interference mechanism responsible for resistance to polytropic leukemia viruses in Mus castaneus
M S Lyu1, A Nihrane, C A Kozak
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20982-0460, USA.
Abstract:
The Asian mouse Mus castaneus is resistant to infection by the polytropic mink cell focus-inducing (MCF) subgroup of murine leukemia viruses (MuLVs). Genetic crosses showed this recessive resistance to be governed by a single gene that maps at or near the gene encoding the polytropic viral receptor, Rmc1. To investigate this resistance, we mated M. castaneus with mice carrying the wild mouse Sxv variant of the Rmc1 receptor that allows infection by xenotropic as well as polytropic virus. Unlike other F1 hybrids of M. castaneus, these F1 mice were resistant to both xenotropic and polytropic classes of MuLVs. Analysis of backcrossed progeny of the F1 hybrids mated to Sxv mice indicates that resistance is due to inheritance of two M. castaneus genes. Cells from individual backcross mice were also examined for cell surface antigen by fluorescence-activated cell sorter analysis with monoclonal antibodies reactive with xenotropic or MCF virus env glycoproteins. A correlation was observed between virus resistance and antigen, suggesting that virus resistance is due to expression of endogenous viral envelope genes that interfere with infection by exogenous virus. Since the inbred strain Rmc1 receptor remains functional in the presence of these M. castaneus genes, and since M. castaneus contains multiple copies of xenotropic MuLV env genes, we suggest that these resistance genes control expression of xenotropic env glycoprotein that interferes with exogenous virus in cells containing the Sxv variant of Rmc1.
Insights
Asian mice (Mus castaneus) exhibit resistance to polytropic murine leukemia viruses (MuLVs). This resistance is linked to endogenous viral genes interfering with exogenous virus infection, particularly in mice with the Sxv variant of the Rmc1 receptor.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- The Asian mouse Mus castaneus displays natural resistance to polytropic mink cell focus-inducing (MCF) subgroup of murine leukemia viruses (MuLVs).
- Previous studies indicated this recessive resistance is controlled by a single gene near the polytropic viral receptor gene, Rmc1.
Purpose of the Study:
- To investigate the genetic basis of Mus castaneus resistance to MuLVs.
- To determine the mechanism by which M. castaneus confers resistance to both xenotropic and polytropic MuLVs.
Main Methods:
- Genetic crosses were performed between M. castaneus and mice with the Sxv variant of the Rmc1 receptor.
- Analysis of backcrossed progeny was conducted.
- Fluorescence-activated cell sorter (FACS) analysis was used to examine cell surface antigens.
Main Results:
- F1 hybrids of M. castaneus and Sxv mice were resistant to both xenotropic and polytropic MuLVs.
- Resistance in backcrossed progeny was linked to two M. castaneus genes.
- A correlation was found between virus resistance and cell surface antigen expression, suggesting endogenous viral envelope glycoproteins interfere with exogenous virus infection.
Conclusions:
- Mus castaneus resistance to MuLVs is controlled by genes regulating xenotropic env glycoprotein expression.
- This expression interferes with exogenous virus infection in cells with the Sxv Rmc1 variant.
- Endogenous viral genes play a role in conferring resistance to specific MuLV subgroups.