Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses.
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 (MDMs) rapidly spread HIV-1 to autologous CD4(+) T cells resulting in productive infection. Transmission takes place across transient adhesive contacts between T cells and MDMs, which have the features of a virological synapse including copolarization of CD4 on the T cell with HIV-1 Gag and Env on the macrophage. We propose that an infected MDM can infect at least one T cell every 6 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.
Groot
Fedde
F
Sir William Dunn School of Pathology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. fedde.groot@path.ox.ac.uk
Welsch
Sonja
S
Sattentau
Quentin J
QJ
D015704:CD4 Antigens / Q000378:metabolism; D002450:Cell Communication; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D015658:HIV Infections / Q000209:etiology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology*
D015704:CD4 Antigens; D015686:Gene Products, env; D015683:Gene Products, gag