Gm. Aldrovandi et Ja. Zack, REPLICATION AND PATHOGENICITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACCESSORY GENE MUTANTS IN SCID-HU MICE, Journal of virology, 70(3), 1996, pp. 1505-1511
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.