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Published on: October 14, 2016

Akvr-1, a dominant murine leukemia virus restriction gene, is polymorphic in leukemia-prone wild mice

M B Gardner, S Rasheed, B K Pal

    Proceedings of the National Academy of Sciences of the United States of America
    |January 1, 1980
    PubMed

    Insights

    A newly identified gene, AKR virus restriction (Akvr-1), in feral mice controls susceptibility to specific retroviruses. The dominant Akvr-1R allele prevents viremia and lymphoma from AKR endogenous retrovirus and other ecotropic viruses.

    Area of Science:

    • Genetics
    • Virology
    • Immunology

    Background:

    • A feral mouse population (Mus musculus domesticus) near Lake Casitas, California, exhibits genetic variation relevant to retroviral resistance.
    • Endogenous retroviruses and murine leukemia viruses can cause significant pathogenesis, including viremia and lymphoma, in susceptible mouse strains.

    Purpose of the Study:

    • To identify and characterize a novel gene conferring resistance to retroviral infections in a feral mouse population.
    • To determine the allelic variants, inheritance pattern, and spectrum of viral restriction mediated by this gene.

    Main Methods:

    • Genetic analysis of a feral mouse population to identify polymorphic alleles.
    • Phenotypic characterization of viral restriction in F1 and backcross hybrids.
    • Testing the restriction efficacy against various retroviruses, including AKR endogenous retrovirus, Moloney murine leukemia virus, and Friend virus.

    Main Results:

    • A restriction gene, AKR virus restriction (Akvr-1), was identified with two alleles: Akvr-1R (restrictive) and Akvr-1r (susceptible).
    • The Akvr-1R allele is dominant and fully prevents AKR endogenous retrovirus viremia and lymphoma in hybrids.
    • Akvr-1R restricts NB-tropic Moloney and Friend viruses but not LC-derived amphotropic retrovirus, suggesting distinct viral targets.

    Conclusions:

    • The Akvr-1 gene provides significant, dominant resistance to specific retroviral infections in mice.
    • The differential restriction pattern indicates that Akvr-1 targets similar elements in ecotropic viruses but not amphotropic viruses.
    • Further investigation into the relationship between Akvr-1 and other known murine restriction loci (Fv-1, Fv-2, Fv-4) is warranted.

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