Viral Piracy: HIV-1 Targets Dendritic Cells for Transmission
Annemarie N. Lekkerkerker, Yvette v. Kooyk and Teunis B.H. Geijtenbeek
Affiliation: Vrije Universiteit MedicalCenter Amsterdam, Department of Molecular Cell Biology andImmunology, v.d. Boechorststraat 7, 1081 BT Amsterdam, TheNetherlands.
Keywords: Dendritic cells, HIV-1 transmission, C-type lectins, DC-SIGN
Dendritic cells (DCs), the professional antigen presenting cells, are critical for host immunity by inducing specific immune responses against a broad variety of pathogens. Remarkably the human immunodeficiency virus-1 (HIV- 1) subverts DC function leading to spread of the virus. At an early phase of HIV-1 transmission, DCs capture HIV-1 at mucosal surfaces and transmit the virus to T cells in secondary lymphoid tissues. Capture of the virus on DCs takes place via C-type lectins of which the dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) is the best studied. DC-SIGN-captured HIV-1 particles accumulate in CD81+ multivesicular bodies (MVBs) in DCs and are subsequently transmitted to CD4+ T cells resulting in infection of T cells. The viral cell-to-cell transmission takes place at the DC-T cell interface termed the infectious synapse. Recent studies demonstrate that direct infection of DCs contributes to the transmission to T cells at a later phase. Moreover, the infected DCs may function as cellular reservoirs for HIV-1. This review discusses the different processes that govern viral piracy of DCs by HIV-1, emphasizing the intracellular routing of the virus from capture on the cell surface to egress in the infectious synapse.
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