AIDS viruses require an intact functional nef gene in order to induce disease. The nonpathogenic molecular cloned virus SIVmac239nef-deletion encodes a truncated nef gene. This attenuated reading frame is expressed both in vitro and in a virus-infected animal in vivo. Encoding the first 58 amino acids of Nef, the reading frame retained its ability to down-modulate CD4 from the surface of T cells. CD4-down-modulated stable cell lines expressing full-length and truncated nef genes were significantly less infected by SIV. SIVmac239nef-open and SIVmacnef-deletion encoding a truncated nef clearly differed in replication kinetics in H9 cells and H9-derived cell lines. SIVmac239nef-deletion replication was delayed in H9. Copyright 1996 S. Karger AG, Basel