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Abstract zur Publikation: CD4- and dynamin-dependent endocytosis of HIV-1 into plasmacytoid dendritic cells

Pritschet K, Donhauser N, Schuster P, Ries M, Haupt S, Kittan NA, Korn K, Pöhlmann S, Holland G, Bannert N et al. (2012): CD4- and dynamin-dependent endocytosis of HIV-1 into plasmacytoid dendritic cells.
Virology 423 (2): 152-164. Epub 2011 Dec 28. doi:10.1016/j.virol.2011.11.026.

Chronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and functional experiments. After attachment to PDC, viruses were taken up in an energy-dependent manner. The virions were located in compartments positive for caveolin; early endosomal antigen 1; Rab GTPases 5, 7 and 9; lysosomal-associated membrane protein 1. PDC harbored more virus in endocytic vesicles than CD4+ T cells (p < 0.05). Blocking CD4 inhibited the uptake of virions into cytosolic and endosomal compartments. Dynasore, an inhibitor of dynamin-dependent endocytosis, not the fusion inhibitor T-20, reduced the HIV-1 induced IFN-alpha production. Altogether, our morphological and functional data support the role of endocytosis for the entry and IFN-alpha induction of HIV-1 in PDC.

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