Isolation and preliminary characterization of Semliki Forest virus mutants with altered pathogenicity for mouse embryos.

Four temperature-sensitive (ts) mutants of the A7 strain of Semliki Forest virus (SFV) have been isolated. All mutants were defective in RNA synthesis at the restrictive temperature (39 degrees C) compared to the permissive temperature (30 degrees C). Since the body temperature of mice fluctuates between 37 degrees C and 39 degrees C, multiplication was also examined at 37 degrees C; only the multiplication of ts4 was restricted. After intraperitoneal infection of 8-day pregnant mice, the wild-type induced rapid abortion. Ts4 and ts26 had no effect on embryonic development. Litters born to ts4-infected mothers developed no postnatal immunity whereas 50% of litters from ts26-infected mothers were immune. Unlike the wild-type, ts14 induced the same or higher virus titres in placental tissue in most mice than in foetal tissue. Ts22 and ts14 induced a range of development defects, including developmental arrest, mummification, abortion and postnatal death. Most surviving offspring were immune. Although ts4 induced no viraemia, ts14, ts22 and ts26 induced a lower titre but longer lasting viraemia than the wild-type. It is concluded that infections of pregnant mice with ts14 and ts22 in particular are good models for analysis of the mechanism of virus-induced developmental defects.