CD4- and dynamin-dependent endocytosis of HIV-1 into plasmacytoid dendritic cells.
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.
Institute of Clinical and Molecular Virology, National Reference Centre for Retroviruses, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Kathrin
K
Pritschet
Norbert
N
Donhauser
Philipp
P
Schuster
Moritz
M
Ries
Sabrina
S
Haupt
Nicolai A
NA
Kittan
Klaus
K
Korn
Stefan
S
Pöhlmann
Gudrun
G
Holland
Norbert
N
Bannert
Elke
E
Bogner
Barbara
B
Schmidt
D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D034281:Dynamins / Q000235:genetics / Q000276:immunology*; D004705:Endocytosis; D011992:Endosomes / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D016253:Microscopy, Immunoelectron
D015704:CD4 Antigens; D016898:Interferon-alpha; D034281:Dynamins