Effects of viral infection on nervous system development. II. Attempts to modify bluetongue-virus-induced malformations with cyclophosphamide and antithymocyte serum.

Treatment with cyclophosphamide and antithymocyte serum (ATS) did not significantly increase the susceptibility of mice to bluetongue virus infections of the nervous system. Cyclophosphamide actually inhibited virus growth in newborn and 2-week-old mice and, in newborn mice, diminished the severity of virus-induced pathologic sequelae. Autoradiographic studies suggested this inhibition resulted from the effect of cyclophosphamide on the immature cells of the subventricular zone which were the cell population selectively infected by bluetongue virus. In newborn mice ATS inhibited the inflammatory reaction and development of antibody, but did not result in alterations in mortality, initial virus growth and localization or early necrosis of cells in the subventricular zone. Antithymocyte serum only caused longer persistence of virus and slight extension of late pathologic lesions. The failure of cyclophosphamide and ATS treatment to induce more extensive lesions in older mice show that the age-dependency of bluetongue lesions is not determined by the immaturity of immune responses.