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Molecular characterization of the Akvr-1 restriction gene: a defective endogenous retrovirus-borne gene identical to
Abstract:
A dominant restriction allele, Akvr-1r, from California wild mice (Mus musculus domesticus) confers resistance to exogenous ecotropic murine leukemia virus (MuLV) infection. The presence of an ecotropic MuLV envelope-related glycoprotein in uninfected virus-resistant cells suggests that viral interference is a possible mechanism for this resistance. We molecularly cloned the ecotropic MuLV envelope-related sequence from the genomic DNA of a wild mouse homozygous for the Akvr-1r locus. The cloned provirus was defective and contained a C-terminal end of the pol gene, a complete envelope gene, and a 3' long terminal repeat. The presence of this provirus was directly correlated with Akvr-1r-mediated virus resistance in cell cultures and hybrid mice. The Akvr-1r provirus restriction map and partial DNA sequence were identical to those of the Fv-4r allele, an ecotropic MuLV resistance locus from Japanese feral mice (M. musculus molossinus), which was previously shown to be allelic with the Akvr-1r gene. The 3' host flanking sequences of Fv-4r and Akvr-1r also had identical restriction maps. These findings indicate that Akvr-1r and Fv-4r are the same gene. It was probably acquired by interbreeding of these feral species in recent times. Conservation of this locus might be favored by the useful function that it performs in protection against ecotropic MuLV infection endemic in both populations of wild mice.
Insights
A specific gene variant in wild mice provides resistance to murine leukemia virus (MuLV) infection. This resistance is linked to a defective provirus, suggesting viral interference as the protection mechanism.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Wild mice possess natural resistance mechanisms against viral infections.
- Murine leukemia virus (MuLV) poses a threat to wild mouse populations.
- Genetic factors play a crucial role in conferring virus resistance.
Purpose of the Study:
- To identify and characterize the genetic basis of resistance to ecotropic MuLV in California wild mice.
- To elucidate the molecular mechanism underlying this virus resistance.
- To compare the resistance locus with known resistance alleles in other wild mouse populations.
Main Methods:
- Molecular cloning of the ecotropic MuLV envelope-related sequence from resistant wild mouse DNA.
- Analysis of the cloned provirus for genetic defects and functional elements.
- Correlation of provirus presence with virus resistance in cell cultures and hybrid mice.
- Restriction mapping and DNA sequencing of the Akvr-1r provirus and flanking regions.
Main Results:
- A defective provirus containing an envelope gene was identified and molecularly cloned from Akvr-1r mice.
- The presence of this provirus directly correlated with resistance to MuLV infection.
- The Akvr-1r provirus exhibited identical restriction maps and DNA sequences to the Fv-4r allele from Japanese mice.
- Host flanking sequences of Akvr-1r and Fv-4r were also identical, indicating they are the same gene.
Conclusions:
- The Akvr-1r locus conferring resistance to MuLV is identical to the Fv-4r allele.
- This resistance likely results from viral interference mediated by the defective provirus.
- The gene was likely acquired through recent interbreeding between different wild mouse subspecies.
- The conservation of this resistance locus is advantageous for protection against endemic MuLV infections.