Characterization of attenuated strains of Rift Valley fever virus

The wild-type ZH501 strain of Rift Valley fever (RVF) virus and two small-plaque strains (T1 and T46) derived from it were characterized by plaque size, pathogenicity for hamsters and ability to replicate in Vero cells. Additionally, a mutagenized, attenuated, large-plaque, vaccine-candidate strain of RVF virus (ZH548-M12) was also studied. Infections with either the ZH501 or T46 strain were uniformly fatal to hamsters. In contrast, nearly all hamsters infected with either the T1 or ZH548-M12 strains survived and were immune to challenge with 10(5) LD50 of the ZH501 strain. Both of these attenuated strains failed to replicate in Vero cells maintained at 41 degrees C, whereas the more virulent strains (ZH501 and T46) replicated at this temperature. The low virulence and ability to induce protection against lethal RVF virus challenge that is associated with the T1 and ZH548-M12 strains make them potential vaccine candidates.