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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
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Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors

A Granelli-Piperno1, B Moser, M Pope

  • 1Theodor Kocher Institute, Bern, Switzerland.

The Journal of Experimental Medicine
|December 1, 1996
PubMed

Insights

Human Immunodeficiency Virus type 1 (HIV-1) efficiently enters dendritic cells (DCs) but does not replicate. This viral entry into DCs is blocked by specific chemokines, highlighting a potential therapeutic target.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Dendritic cells (DCs) play a crucial role in immune responses.
  • HIV-1 replication is typically studied in T cells, with DC infection being less understood.
  • Previous studies faced challenges in demonstrating substantial mature DC infection by HIV-1.

Purpose of the Study:

  • To investigate the efficiency of HIV-1 entry and early reverse transcription in mature dendritic cells.
  • To compare HIV-1 interaction with DCs versus T cells.
  • To explore the role of chemokine receptors in HIV-1 entry into DCs.

Main Methods:

  • Coculture of mature dendritic cells (DCs) and T cells with HIV-1.
  • Assessment of HIV-1 reverse transcription products (early and late) using molecular techniques.
  • Analysis of viral entry inhibition by chemokines (RANTES, SDF-1) and their corresponding receptors (CCR5, CXCR4).
  • Evaluation of viral entry in DCs from individuals with non-functional CCR5 receptors.

Main Results:

  • HIV-1 initiates reverse transcription more efficiently in DCs than in T cells, despite lower CD4 and gp120 expression on DCs.
  • While early reverse transcription products are formed efficiently, late gag-containing sequences are scarce, indicating limited active replication in DCs.
  • Viral entry into DCs is mediated by chemokine receptors CCR5 (for M-tropic strains) and CXCR4 (for T-tropic strain IIIB), and can be blocked by corresponding chemokines.

Conclusions:

  • Mature dendritic cells actively internalize HIV-1, evidenced by efficient early reverse transcription.
  • HIV-1 replication is significantly restricted in mature DCs.
  • Chemokine receptors CCR5 and CXCR4 are critical for HIV-1 entry into DCs, presenting potential targets for blocking viral transmission.

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