Retroviral spongiform polioencephalomyelopathy.

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.