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Poliovirus infection of cyclophosphamide- treated mice results in persistence and late paralysis

I. Clinical, pathologic, and immunologic studies

From The Les Turner ALS Research Laboratory, Department of Neurology, Northwestern University Medical School.

An attenuated human poliovirus infection of cyclophosphamide (CY)-treated mice was developed as a model of persistent CNS enterovirus infections and as an investigation of the interaction of virus with motor neurons during persistence. Ten percent of mice inoculated intracerebrally with undiluted virus developed clinical disease by day 90, but of those treated with CY, 80% developed disease. At higher virus dilutions plus CY there was a marked increase in the incubation period. The latest onset of clinical disease occurred on day 146. Only paralyzed animals had pathologic changes in the spinal cord and virus antigen in anterior horn cells. Neutralizing antibodies were suppressed by CY, as were humoral and cellular immune responses to other antigens.

Address correspondence and reprint requests to Dr. Jubelt. Department of Neurology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611.

This work was supported by a Basic Research Grant from the Muscular Dystrophy Association, grant RR-05370 from the US Public Health Service, National Institutes of Health, and Dr. Jubelt's Teacher-Investigator Development Award (No. 5-KO7NS00573) from the NINCDS, US Public Health Service.

Presented in part at the 34th Annual Meeting of the American Academy of Neurology, Washington, DC, April 1982.

Accepted for publication July 28, 1983.