SDF-1/CXCL12 Production by Mature Dendritic Cells Inhibits the Propagation of X4-Tropic HIV-1 Isolates at the Dendritic Cell-T-Cell Infectious Synapse

AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain.
Journal of Virology (Impact Factor: 4.44). 02/2010; 84(9):4341-51. DOI: 10.1128/JVI.02449-09
Source: PubMed


An efficient mode of HIV-1 infection of CD4 lymphocytes occurs in the context of infectious synapses, where dendritic cells
(DCs) enhance HIV-1 transmission to lymphocytes. Emergence of CXCR4-using (X4) HIV-1 strains occurs late in the course of
HIV-1 infection, suggesting that a selective pressure suppresses the switch from CCR5 (R5) to X4 tropism. We postulated that
SDF-1/CXCL12 chemokine production by DCs could be involved in this process. We observed CXCL12 expression by DCs in vivo in the parafollicular compartment of lymph nodes. The role of mature monocyte-derived dendritic cells (mMDDCs) in transmitting
R5 and X4 HIV-1 strains to autologous lymphocytes was studied using an in vitro infection system. Using this model, we observed a strong enhancement of lymphocyte infection with R5, but not with X4, viruses.
This lack of DC-mediated enhancement in the propagation of X4 viruses was proportional to CXCL12 production by mMDDCs. When
CXCL12 activity was inhibited with specific neutralizing antibodies or small interfering RNAs (siRNAs), the block to mMDDC
transfer of X4 viruses to lymphocytes was removed. These results suggest that CXCL12 production by DCs resident in lymph nodes
represents an antiviral mechanism in the context of the infectious synapse that could account for the delayed appearance of
X4 viruses.

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