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Immunosuppression and murine polyomavirus infection
1Department of Medical Microbiology, University of Wisconsin Medical School, Madison.
Abstract:
Murine polyomavirus (MPYV) infection in mice has many similarities to human infections by BK virus (BKV) and JC virus (JCV) and provides a model for the human infections. MPYV causes acute, inapparent infection with virus appearing in numerous organs, including brain and kidney, and then subsides and becomes latent. At a later time it can be reactivated by corticosteroid treatment or pregnancy (McCance and Mims, 1979, McCance, 1983). To determine the effect of prolonged immunosuppression on virus activity in brain and kidney during acute infection, mice were treated with methotrexate, cyclophosphamide, or prednisone and azathioprine and inoculated with murine polyomavirus. Prednisone/azathioprine and cyclophosphamide caused protracted kidney infection and methotrexate had no effect. In the brain, prednisone/azathioprine and cyclophosphamide had minor effects on virus titers and course of infection, but methotrexate prevented MPYV from appearing in the brain. When mice were immunosuppressed with prednisone/azathioprine one week prior to inoculation, titers were much higher in the kidneys, but virus did not appear in the brain until late in the course of infection.
Insights
Murine polyomavirus (MPYV) infection in mice, a model for human polyomaviruses, showed varied effects of immunosuppression. Methotrexate prevented brain infection, while other drugs prolonged kidney infections.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Murine polyomavirus (MPYV) infection in mice serves as a model for human BK virus (BKV) and JC virus (JCV) infections.
- MPYV infection is typically acute and inapparent, with the virus becoming latent and potentially reactivated later.
- Understanding the impact of immunosuppression on MPYV reactivation is crucial for modeling human polyomavirus infections.
Purpose of the Study:
- To investigate the effects of prolonged immunosuppression on murine polyomavirus (MPYV) activity in the brain and kidney during acute infection.
- To compare the efficacy of different immunosuppressive agents (methotrexate, cyclophosphamide, prednisone/azathioprine) in controlling MPYV infection.
Main Methods:
- Mice were inoculated with murine polyomavirus (MPYV) and treated with immunosuppressive drugs: methotrexate, cyclophosphamide, or prednisone and azathioprine.
- Virus activity in the brain and kidney was monitored during acute infection.
- One group of mice received prednisone/azathioprine treatment one week prior to MPYV inoculation.
Main Results:
- Prednisone/azathioprine and cyclophosphamide treatments resulted in protracted kidney infections.
- Methotrexate treatment had no significant effect on kidney infection.
- Methotrexate prevented MPYV from appearing in the brain, while prednisone/azathioprine and cyclophosphamide had minor effects on brain virus titers.
- Pre-inoculation immunosuppression with prednisone/azathioprine led to higher kidney titers and delayed brain infection.
Conclusions:
- Different immunosuppressive agents have distinct effects on MPYV distribution and viral load in the brain and kidney.
- Methotrexate demonstrates a specific inhibitory effect on MPYV neuroinvasion.
- The timing and type of immunosuppression significantly influence the course of MPYV infection, highlighting the complexity of managing viral reactivation in immunocompromised states.