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Viral Tracing of Genetically Defined Neural Circuitry
13:06

Viral Tracing of Genetically Defined Neural Circuitry

Published on: October 17, 2012

Retroviral spongiform polioencephalomyelopathy

M B Gardner

    Reviews of Infectious Diseases
    |January 1, 1985
    PubMed

    Insights

    Aging wild mice develop paralysis and lymphoma due to a naturally occurring murine leukemia virus (MuLV). Genetic resistance to this virus is controlled by a dominant gene, offering insights into retroviral diseases.

    Area of Science:

    • Virology
    • Immunology
    • Neurology
    • Oncology

    Background:

    • Aging wild mice in Southern California exhibit a high incidence of hind-leg paralysis and lymphoma.
    • These conditions are linked to an indigenous ecotropic murine leukemia virus (MuLV), leading to persistent viremia and immunologic tolerance.
    • Pathological findings include spongiform changes, gliosis, and neuronal loss in the spinal cord, primarily caused by abortive viral replication.

    Purpose of the Study:

    • To investigate the cause and mechanisms of naturally occurring paralytic disease and lymphoma in aging wild mice.
    • To identify the genetic factors controlling susceptibility and resistance to MuLV-induced diseases.
    • To establish an experimental model for studying retroviral-induced neurodegeneration and oncogenesis.

    Main Methods:

    • Characterization of pathological features in naturally affected wild mice.
    • Identification and genetic analysis of the ecotropic murine leukemia virus (MuLV).
    • Experimental inoculation of laboratory mice with cloned MuLV to reproduce the disease.

    Main Results:

    • A specific ecotropic MuLV was identified as the causative agent for both paralysis and lymphoma in wild mice.
    • Genetic control of disease susceptibility was mapped to a dominant ecotropic virus restriction gene, Akvr-1R/Fv-4R.
    • Experimental inoculation successfully replicated the natural disease, confirming MuLV's role and providing a model for further study.

    Conclusions:

    • Ecotropic MuLV infection is the direct cause of paralytic disease and lymphoma in aging wild mice.
    • The Akvr-1R/Fv-4R gene plays a crucial role in conferring resistance to MuLV-induced pathologies.
    • This naturally occurring retroviral disease serves as a valuable model for understanding virus-induced neuronal and glial cell degeneration.

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