PATHOGENICITY OF LIVE, ATTENUATED SIV AFTER MUCOSAL INFECTION OF NEONATAL MACAQUES

Adult macaques do not develop disease after infection with a nef delet ion mutant of the simian immunodeficiency virus (SIV) and are protecte d against challenge with pathogenic virus. This finding led to the pro posal to use nef-deleted viruses as live, attenuated vaccines to preve nt human acquired immunodeficiency syndrome (AIDS). In contrast, neona tal macaques developed persistently high levels of viremia after oral exposure to an SIV nef, vpr, and negative regulatory element (NRE) del etion mutant. Severe hemolytic anemia, thrombocytopenia, and CD4(+) T cell depletion were observed, indicating that neither nef nor vpr dete rmine pathogenicity in neonates. Because such constructs have retained their pathogenic potential, they should not be used as candidate live , attenuated virus vaccines against human AIDS.