Nef enhances HIV-1 infectivity via association with the virus assembly complex.
The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle.
Qi
Mingli
M
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A-5301 Medical Center North, Nashville, TN 37232-2363, USA.
Aiken
Christopher
C
D019943:Amino Acid Substitution; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D015754:Genes, nef; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics / Q000502:physiology; D019065:Virus Assembly / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D016572:Cyclosporine; D021984:Cyclophilin A