The Protein Network of HIV Budding

Cell. 2003 Sep 19;114(6):701-13. doi: 10.1016/s0092-8674(03)00714-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Compartmentation / genetics
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cell Membrane / virology*
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport
  • Endosomes / genetics
  • Endosomes / metabolism
  • Endosomes / ultrastructure
  • Gene Products, gag / metabolism
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • HIV-1 / ultrastructure
  • Humans
  • Microfilament Proteins / metabolism
  • Microscopy, Electron
  • Models, Biological
  • Mutation / genetics
  • Protein Binding / physiology
  • Proteins / metabolism*
  • Transcription Factors / metabolism
  • Transport Vesicles / metabolism
  • Transport Vesicles / ultrastructure
  • Transport Vesicles / virology*
  • Viral Proteins / metabolism
  • Virus Shedding / physiology*
  • gag Gene Products, Human Immunodeficiency Virus

Substances

  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Gene Products, gag
  • Microfilament Proteins
  • Proteins
  • Transcription Factors
  • Tsg101 protein
  • Viral Proteins
  • actin interacting protein 1
  • gag Gene Products, Human Immunodeficiency Virus
  • p6 gag protein, Human immunodeficiency virus 1