Nucleocapsid Promotes Localization of HIV-1 gag to uropods that participate in virological synapses between T Cells

G. Nicholas Llewellyn, Ian Hogue, Jonathan R. Grover, Akira Ono

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. Infected T cells formed contacts with uninfected target T cells preferentially via HIV-1 Gag-containing uropods compared to leading edges that lack plasma-membrane-associated Gag. Cell contacts enriched in Gag and CD4, which define the virological synapse (VS), are also enriched in uropod markers. These results indicate that Gag-laden uropods participate in the formation and/or structure of the VS, which likely plays a key role in cell-to-cell transmission of HIV-1. Consistent with this notion, a myosin light chain kinase inhibitor, which disrupts uropods, reduced virus particle transfer from infected T cells to target T cells. Mechanistically, we observed that Gag copatches with antibody-crosslinked uropod markers even in non-polarized cells, suggesting an association of Gag with uropod-specific microdomains that carry Gag to uropods. Finally, we determined that localization of Gag to the uropod depends on higher-order clustering driven by its NC domain. Taken together, these results support a model in which NC-dependent Gag accumulation to uropods establishes a preformed platform that later constitutes T-cell-T-cell contacts at which HIV-1 virus transfer occurs.

Original languageEnglish (US)
Article numbere1001167
JournalPLoS Pathogens
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Nucleocapsid
Synapses
HIV-1
T-Lymphocytes
Viruses
Myosin-Light-Chain Kinase
Life Cycle Stages
Virion
Cluster Analysis
Cell Membrane
Lymphocytes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Nucleocapsid Promotes Localization of HIV-1 gag to uropods that participate in virological synapses between T Cells. / Nicholas Llewellyn, G.; Hogue, Ian; Grover, Jonathan R.; Ono, Akira.

In: PLoS Pathogens, Vol. 6, No. 10, e1001167, 01.10.2010.

Research output: Contribution to journalArticle

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