The protein network of HIV budding.
HIV release requires TSG101, a cellular factor that sorts proteins into vesicles that bud into multivesicular bodies (MVB). To test whether other proteins involved in MVB biogenesis (the class E proteins) also participate in HIV release, we identified 22 candidate human class E proteins. These proteins were connected into a coherent network by 43 different protein-protein interactions, with AIP1 playing a key role in linking complexes that act early (TSG101/ESCRT-I) and late (CHMP4/ESCRT-III) in the pathway. AIP1 also binds the HIV-1 p6(Gag) and EIAV p9(Gag) proteins, indicating that it can function directly in virus budding. Human class E proteins were found in HIV-1 particles, and dominant-negative mutants of late-acting human class E proteins arrested HIV-1 budding through plasmal and endosomal membranes. These studies define a protein network required for human MVB biogenesis and indicate that the entire network participates in the release of HIV and probably many other viruses.
D000818:Animals; D019556:COS Cells; D002451:Cell Compartmentation / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015683:Gene Products, gag / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism; D017201:Virus Shedding / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag; D008840:Microfilament Proteins; D011506:Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099177:Tsg101 Protein; C115237:actin interacting protein 1; C083002:p6 gag protein, Human immunodeficiency virus 1