Author/Authors :
Uta K. von Schwedler، نويسنده , , Melissa Stuchell، نويسنده , , Barbara Müller، نويسنده , , Diane M. Ward، نويسنده , , Hyo Young Chung، نويسنده , , Eiji Morita، نويسنده , , Hubert E. Wang، نويسنده , , Thaylon Davis، نويسنده , , Gong-Ping He، نويسنده , , Daniel M. Cimbora، نويسنده , , J. Anna Scott، نويسنده , , Hans-Georg Kr?usslich، نويسنده , , Jerry Kaplan، نويسنده , , Scott G. Morham، نويسنده , , Wesley I. Sundquist، نويسنده ,
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 p6Gag and EIAV p9Gag 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.
