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Host genes conferring resistance to a central nervous system disease induced by a polytropic recombinant Friend
R S Buller1, K Wehrly, J L Portis
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Abstract:
Infection of certain strains of mice with the ecotropic Friend murine leukemia virus results in the generation of recombinant polytropic mink cell focus-inducing viruses and the development of erythroleukemia. We isolated a Friend mink cell focus-inducing virus (F-MCF-98D) from a Friend murine leukemia virus-infected BALB/c mouse which caused primarily a neurological disease as well as a low incidence of leukemia in susceptible IRW mice. Through genetic studies with the resistant C57BL/10 strain, we identified two genes which correlated with restricted viral replication and resistance to the development of disease caused by F-MCF-98D. One gene correlated with the expression of an endogenous gp70 linked to the Rmcf gene and might act by viral interference. The mechanism of action of the second gene was less clear, but it appeared to be associated with development of an antiviral antibody response.
Insights
Genetic studies identified two genes in mice that restrict Friend-MCF-98D virus replication and prevent disease. One gene involves viral interference, while the second is linked to antibody response.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Friend murine leukemia virus (FMLV) infection can lead to erythroleukemia and generate recombinant polytropic mink cell focus-forming (MCF) viruses.
- A specific isolate, F-MCF-98D, derived from FMLV-infected BALB/c mice, induces neurological disease and some leukemia in susceptible IRW mice.
Purpose of the Study:
- To identify host genetic factors conferring resistance to F-MCF-98D virus-induced disease.
- To understand the mechanisms underlying resistance to viral replication and pathogenesis.
Main Methods:
- Genetic crosses between susceptible IRW mice and resistant C57BL/10 mice.
- Analysis of viral replication and disease development in different mouse strains.
- Correlation of resistance with specific gene expression and immune responses.
Main Results:
- Two distinct genes were identified that correlate with restricted F-MCF-98D viral replication and resistance to disease.
- One resistance gene is linked to the expression of an endogenous gp70, potentially acting via viral interference.
- The second gene's mechanism is less defined but appears associated with the development of an antiviral antibody response.
Conclusions:
- Host genetics play a crucial role in determining susceptibility or resistance to F-MCF-98D virus-induced neurological disease and leukemia.
- Viral interference and antibody-mediated immune responses are key mechanisms conferring genetic resistance to this retrovirus.