Nef from human immunodeficiency virus type 1(F12) inhibits viral production and infectivity.
Human immunodeficiency virus type 1(F12) (HIV-1(F12)) interferes with the replication of other strains of HIV. Its accessory protein, Nef, is sufficient for this phenotype, where the production and infectivity of HIV are impaired significantly. The analysis of three rare mutations in this Nef protein revealed that these effects could be separated genetically. Moreover, the defect in virus production correlated with the lack of processing of the p55(Gag) precursor in the presence of Nef from HIV-1(F12). Importantly, the introduction of one of these mutations (E177G) into Nef from HIV-1(NL4-3) also created a dominant-negative Nef protein. Effects of Nef from HIV-1(F12) on virus production and Gag processing correlated with its altered subcellular distribution. Moreover, the association with two new cellular proteins with molecular masses of 74 and 75 kDa, which do not interact with other Nef proteins, correlated with the decreased virion infectivity. The identification of a dominant-negative protein for the production and infectivity of HIV suggests that Nef plays an active role at this stage of the viral replicative cycle.
Fackler
O T
OT
Department of Medicine, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94143-0703, USA.
d'Aloja
P
P
Baur
A S
AS
Federico
M
M
Peterlin
B M
BM
D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D015683:Gene Products, gag / Q000378:metabolism; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014162:Transfection; D014774:Virulence; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D016827:CD8 Antigens; D015683:Gene Products, gag; D015693:Gene Products, nef; D011498:Protein Precursors; D011506:Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C059767:p55 gag precursor protein, Human immunodeficiency virus 1