Progressive disease after HIV infection is inversely correlated with the presence of plasmacytoid dendritic cells (pDCs), a subset of the dendritic cell family and the major producers of type 1 interferon in the body. A JCI paper reports the mechanisms by which HIV-1 activates human pDCs. By identifying the active component of HIV-1 that stimulates pDC function, and consequently other antigen presenting cell function, DC function can be targeted in the design of efficient vaccines or immunotherapies for HIV..
The authors show that pDC activation by HIV-1 requires at least two interactions between the cell and virus. Initially, envelope-CD4 interactions mediate the endocytosis of HIV-1. Next, viral nucleic acids, particularly RNA, stimulate pDCs through Toll-like receptors.
A decrease of blood pDC frequency is typically observed in chronic infections due to HIV-1 and correlates with high viral load, reduced CD4 counts and susceptibility to opportunistic infections, and is only partially reverted by anti-retroviral therapy. By identifying the active component of HIV-1 which stimulates pDC function, and consequently other antigen presenting cell function, the authors have recognized an important pathway whereby DC function can be targeted in the design of efficient vaccines or immunotherapies for HIV.
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TITLE: Endocytosis of HIV-1 Activates Plasmacytoid Dendritic Cells via Toll-Like Receptor -viral RNA interactions
