Volume 8 Supplement 2

Frontiers of Retrovirology 2011

Open Access

The regulated secretory pathway in CD4+T cells contributes to HIV-1 transmission at the virological synapse

  • Clare Jolly1,
  • Sonja Welsch2, 3,
  • Stefanie Michor4 and
  • Quentin J Sattentau4
Retrovirology20118(Suppl 2):P35

https://doi.org/10.1186/1742-4690-8-S2-P35

Published: 3 October 2011

Direct cell-cell spread of Human Immunodeficiency Virus type-1 (HIV-1) at the virological synapse (VS) is an efficient mode of dissemination between CD4+ T cells but the mechanisms by which HIV-1 proteins are directed towards intercellular contacts is unclear. We have used confocal microscopy and electron tomography coupled with functional virology and cell biology of primary CD4+T cells from normal individuals and patients with Chediak Higashi Syndrome and report that the HIV-1 VS displays a regulated secretion phenotype that shares features with polarised secretion at the T cell immunological synapse (IS). Cell-cell contact at the VS re-orientates the microtubule organising center (MTOC) and organelles within the HIV-1-infected T cell towards the engaged target T cell, concomitant with polarisation of viral proteins. Directed secretion of proteins at the T cell IS requires specialised organelles termed secretory lysosomes (SL) and we show that the HIV-1 envelope glycoprotein (Env) localises with CTLA-4 and FasL in SL-related compartments and at the VS. Finally, CD4+ T cells that are disabled for regulated secretion are less able to support productive cell-to-cell HIV-1 spread. We propose that HIV-1 hijacks the regulated secretory pathway of CD4+T cells to enhance its dissemination by cell-cell spread.

Authors’ Affiliations

(1)
Medical Division of Infection and Immunity, University College London
(2)
WellcomeTrust Centre for Human Genetics Division of Structural Biology, University of Oxford
(3)
Structural and Computational Biology Unit, European Molecular Biology Laboratory
(4)
The Sir William Dunn School of Pathology, University of Oxford

Copyright

© Jolly et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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