The protein network of HIV budding

Uta K. Von Schwedler, Melissa Stuchell, Barbara Müller, Diane M. Ward, Hyo Young Chung, Eiji Morita, Hubert E. Wang, Thaylon Davis, Gong Ping He, Daniel M. Cimbora, Anna Scott, Hans Georg Kräusslich, Jerry Kaplan, Scott G. Morham, Wesley I. Sundquist

Research output: Contribution to journalArticle

653 Scopus citations

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.

Original languageEnglish
Pages (from-to)701-713
Number of pages13
JournalCell
Volume114
Issue number6
DOIs
StatePublished - Sep 19 2003
Externally publishedYes

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    Von Schwedler, U. K., Stuchell, M., Müller, B., Ward, D. M., Chung, H. Y., Morita, E., Wang, H. E., Davis, T., He, G. P., Cimbora, D. M., Scott, A., Kräusslich, H. G., Kaplan, J., Morham, S. G., & Sundquist, W. I. (2003). The protein network of HIV budding. Cell, 114(6), 701-713. https://doi.org/10.1016/S0092-8674(03)00714-1