Trans-dominant cellular inhibition of DC-SIGN-mediated HIV-1 transmission.
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.
Wu
Li
L
Model Development Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. liwu@ncifcrf.gov
Martin
Thomas D
TD
Han
Yoon-Chi
YC
Breun
Sabine K J
SK
KewalRamani
Vineet N
VN
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000635:transmission*; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D014162:Transfection; D014779:Virus Replication
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human