Submitted December 19, 2007
Accepted February 20, 2008
Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses
Fedde Groot*, Sonja Welsch, and Quentin J. Sattentau
The Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
* Corresponding author; email: fedde.groot{at}path.ox.ac.uk.
Macrophages are reservoirs of HIV-1 infection, proposed to transmit virus to CD4+ T cells, the primary target of the virus. Here we report that human monocyte-derived macrophages (MDM) rapidly spread HIV-1 to autologous CD4+ T cells resulting in productive infection. Transmission takes place across transient adhesive contacts between T cells and MDM, which have the features of a virological synapse including co-polarization of CD4 on the T cell with HIV-1 Gag and Env on the MDM. We propose that an infected MDM can infect at least one T cell every six hours. Since HIV-1-infected macrophages can survive for many weeks, these results highlight the central role played by macrophages in HIV-1 infection and pathogenesis.
