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 the SCID-hu model system, we have examined the infectivity, replicative capacity, and pathogenicity of strains of the molecular clone HIV-1NL4-3 that contain deletion mutations in these individual accessory genes. We determined that deletion of these genes had differential effects on both infectivity and pathogenicity. Deletion of vpr had little or no effect on viral infectivity, replication, and pathogenicity; however, deletion of vpu or vif had a significant effect on infectivity and moderate effects on pathogenicity. nef-minus strains were the most attenuated in this system, demonstrating significantly lower levels of infectivity and pathogenicity. However, deletion of these individual genes attenuated but did not abrogate the pathogenic properties of HIV-1. Mutant viruses still retained the ability to induce thymocyte depletion to various degrees if implants were infected with higher doses of virus or observed for longer periods of time. The relative contributions of these genes to in vivo pathogenic potential should be taken into consideration when one is contemplating a live attenuated vaccine for HIV-1.
Aldrovandi
G M
GM
Department of Medicine, UCLA School of Medicine, USA.
Zack
J A
JA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral; D004195:Disease Models, Animal; D017353:Gene Deletion; D015693:Gene Products, nef / Q000235:genetics; D016346:Gene Products, vif / Q000235:genetics; D016336:Gene Products, vpr / Q000235:genetics; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D004279:DNA, Viral; D015693:Gene Products, nef; D016346:Gene Products, vif; D016336:Gene Products, vpr; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins