REPLICATION AND PATHOGENICITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACCESSORY GENE MUTANTS IN SCID-HU MICE

The functional roles of the human immunodeficiency virus type 1 (HIV-1 ) accessory genes (nef, vpr, vpu, and vif) are as yet unclear. Using t he SCID-hu model system, we have examined the infectivity, replicative capacity, and pathogenicity of strains of the molecular clone HIV-1(N L4-3) that contain deletion mutations in these individual accessory ge nes. We determined that deletion of these genes had differential effec ts on both infectivity and pathogenicity. Deletion of vpr had little o r no effect on viral infectivity, replication, and pathogenicity; howe ver, deletion of vpu or vif had a significant effect on infectivity an d moderate effects on pathogenicity. nef-minus strains were the most a ttenuated in this system, demonstrating significantly lower levels of infectivity and pathogenicity. However, deletion of these individual g enes attenuated but did not abrogate the pathogenic properties of HIV- 1. Mutant viruses still retained the ability to induce thymocyte deple tion to various degrees if implants were infected with higher doses of virus or observed for longer periods of time. The relative contributi ons of these genes to in vivo pathogenic potential should be taken int o consideration when one is contemplating a live attenuated vaccine fo r HIV-1.