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.
Mesh Terms:
Animals, COS Cells, Cell Compartmentation, Cell Line, Cell Membrane, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Endosomes, Gene Products, gag, HIV-1, Humans, Microfilament Proteins, Microscopy, Electron, Models, Biological, Mutation, Protein Binding, Proteins, Transcription Factors, Transport Vesicles, Viral Proteins, Virus Shedding, gag Gene Products, Human Immunodeficiency Virus
Animals, COS Cells, Cell Compartmentation, Cell Line, Cell Membrane, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Endosomes, Gene Products, gag, HIV-1, Humans, Microfilament Proteins, Microscopy, Electron, Models, Biological, Mutation, Protein Binding, Proteins, Transcription Factors, Transport Vesicles, Viral Proteins, Virus Shedding, gag Gene Products, Human Immunodeficiency Virus
Cell
Date: Sep. 19, 2003
PubMed ID: 14505570
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