Journal article
Trans-dominant cellular inhibition of DC-SIGN-mediated HIV-1 transmission
Retrovirology, Vol.1(1), pp.14-14
06/28/2004
DOI: 10.1186/1742-4690-1-14
PMID: 15222882
Abstract
Background: Dendritic cell (DC) transmission of human immunodeficiency virus (HIV) to CD4+ T cells occurs across a point of cell-cell contact referred to as the infectious synapse. The relationship between the infectious synapse and the classically defined immunological synapse is not currently understood. We have recently demonstrated that human B cells expressing exogenous DC-SIGN, DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin, efficiently transmit captured HIV type 1 (HIV-1) to CD4+ T cells. K562, another human cell line of hematopoietic origin that has been extensively used in functional analyses of DC-SIGN and related molecules, lacks the principal molecules involved in the formation of immunological synaptic junctions, namely major histocompatibility complex (MHC) class II molecules and leukocyte function-associated antigen-1 (LFA-1). We thus examined whether K562 erythroleukemic cells could recapitulate efficient DC-SIGN-mediated HIV-1 transmission (DMHT).
Results: Here we demonstrate that DMHT requires cell-cell contact. Despite similar expression of functional DC-SIGN, K562/DC-SIGN cells were inefficient in the transmission of HIV-1 to CD4+ T cells when compared with Raji/DC-SIGN cells. Expression of MHC class II molecules or LFA-1 on K562/DC-SIGN cells was insufficient to rescue HIV-1 transmission efficiency. Strikingly, we observed that co-culture of K562 cells with Raji/DC-SIGN cells impaired DMHT to CD4+ T cells. The K562 cell inhibition of transmission was not directly exerted on the CD4+ T cell targets and required contact between K562 and Raji/DC-SIGN cells.
Conclusions: DMHT is cell type dependent and requires cell-cell contact. We also find that the cellular milieu can negatively regulate DC-SIGN transmission of HIV-1 in trans.
Details
- Title: Subtitle
- Trans-dominant cellular inhibition of DC-SIGN-mediated HIV-1 transmission
- Creators
- Li Wu - Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USAThomas D Martin - Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USAYoon-Chi Han - Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USASabine KJ Breun - Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USAVineet N KewalRamani - Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
- Resource Type
- Journal article
- Publication Details
- Retrovirology, Vol.1(1), pp.14-14
- Publisher
- BioMed Central; London
- DOI
- 10.1186/1742-4690-1-14
- PMID
- 15222882
- ISSN
- 1742-4690
- eISSN
- 1742-4690
- Language
- English
- Date published
- 06/28/2004
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002391802771
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