One of the most exciting recent developments in the field of retroviruses is the finding that their Gag proteins hijack cellular proteins from the mutivesicular body (MVB) pathway during the budding process. The Gag proteins of oncoretroviruses possess a PPxY motif that recruits a ubiquitin ligase from the Nedd4 family, whereas those of the human immunodeficiency virus interact through a PTAP motif with Tsg101, a protein of the ESCRT-1 complex. It is currently assumed that Nedd4 and Tsg101 represent equivalent entry gates towards the same cellular process leading to budding, and that both partners are recruited to the plasma membrane where viral budding occurs. However, we report here that the budding of the human oncoretrovirus HTLV-1, the Gag proteins of which possess tandem PPPY/PTAP motifs, requires both Nedd4 and Tsg101. We show that Nedd4.1, but not Nedd4.2, is recruited by the PPPY motif of Gag and subsequently catalyzes Gag ubiquitination. We also demonstrate that Gag interacts first with Nedd4.1 at the plasma membrane and then with Tsg101 in late endosomes/MVBs. Consistently, we found that HTLV-1 particles mutated in the PPPY motif remain underneath the plasma membrane, blocked at an early step of the budding process, whereas PTAP-mutated viruses accumulate in intracellular vesicles, blocked at a later step. Our findings indicate that Nedd4.1 and Tsg101 act successively in the assembly process of HTLV-1 to ensure proper Gag trafficking through the endocytic pathway up to late endosomes where the late steps of retroviral release occur.
Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding Available to Purchase
Vincent Blot, Fabien Perugi, Bernard Gay, Marie-Christine Prévost, Laurence Briant, Frédéric Tangy, Hugues Abriel, Olivier Staub, Marie-Christine Dokhélar, Claudine Pique; Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. J Cell Sci 1 May 2004; 117 (11): 2357–2367. doi: https://doi.org/10.1242/jcs.01095
Download citation file:
Sign in
Client Account
Sign in via your institution
Sign in via ShibbolethAdvertisement
Special Issue – Cell Biology of Mitochondria

Our special issue on ‘Cell Biology of Mitochondria’ is now complete. Explore this issue and read the Editorial from our Guest Editors Ana J. García-Sáez and Heidi McBride.
Save the date – Imaging Cell Dynamics

We are delighted to announce that we will be hosting a 2026 Imaging Cell Dynamics meeting. This meeting will provide a unique opportunity to bring together experts working at the interface between cell biology and imaging. Save the date for 11-14 May 2026 and register for more information.
Mitochondria–membranous organelle contacts at a glance

Antigoni Diokmetzidou and Luca Scorrano provide an overview of contacts between mitochondria and other membranous organelles, describing the interorganelle tethers involved and the factors that regulate the composition and functions of such contacts.
JCS-FocalPlane Training Grants

Early-career researchers - working in an area covered by JCS - who would like to attend a microscopy training course, please apply. Deadline dates for 2025 applications: 6 June 2025 (decision by week commencing 28 July 2025) and 5 September 2025 (decision by week commencing 20 October 2025).
JCS fast-track option

Have a paper that has been reviewed elsewhere? JCS is pleased to consider such manuscripts for fast-tracked decision making. Send us your manuscript together with the full set of reviews and decision letters, and we will make an initial decision within one week.
Help shape your future publishing experience

We are gathering feedback from our readers, authors and reviewers, to help us shape the next 100 years and to keep offering a publishing experience that truly supports our community. Please have your say by completing our community survey. Survey closes on 25 June.