Selective transmission of R5 HIV-1 over X4 HIV-1 at the dendritic cell-T cell infectious synapse is determined by the T cell activation state

PLoS Pathog. 2009 Jan;5(1):e1000279. doi: 10.1371/journal.ppat.1000279. Epub 2009 Jan 30.


Dendritic cells (DCs) are essential antigen-presenting cells for the induction of T cell immunity against HIV. On the other hand, due to the susceptibility of DCs to HIV infection, virus replication is strongly enhanced in DC-T cell interaction via an immunological synapse formed during the antigen presentation process. When HIV-1 is isolated from individuals newly infected with the mixture of R5 and X4 variants, R5 is predominant, irrespective of the route of infection. Because the early massive HIV-1 replication occurs in activated T cells and such T-cell activation is induced by antigen presentation, we postulated that the selective expansion of R5 may largely occur at the level of DC-T cell interaction. Thus, the immunological synapse serves as an infectious synapse through which the virus can be disseminated in vivo. We used fluorescent recombinant X4 and R5 HIV-1 consisting of a common HIV-1 genome structure with distinct envelopes, which allowed us to discriminate the HIV-1 transmitted from DCs infected with the two virus mixtures to antigen-specific CD4(+) T cells by flow cytometry. We clearly show that the selective expansion of R5 over X4 HIV-1 did occur, which was determined at an early entry step by the activation status of the CD4(+) T cells receiving virus from DCs, but not by virus entry efficiency or productivity in DCs. Our results imply a promising strategy for the efficient control of HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Flow Cytometry
  • Gene Expression Regulation
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Immunological Synapses / immunology
  • Immunological Synapses / virology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lymphocyte Activation*
  • Microscopy, Fluorescence
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*


  • CXCR4 protein, human
  • Luminescent Proteins
  • Receptors, CCR5
  • Receptors, CXCR4
  • enhanced green fluorescent protein
  • fluorescent protein 583
  • Green Fluorescent Proteins