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- Title
HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells.
- Authors
Gringhuis, Sonja I; van der Vlist, Michiel; van den Berg, Linda M; den Dunnen, Jeroen; Litjens, Manja; Geijtenbeek, Teunis B H
- Abstract
Pattern-recognition receptors (PRRs) elicit antiviral immune responses to human immunodeficiency virus type 1 (HIV-1). Here we show that HIV-1 required signaling by the PRRs Toll-like receptor 8 (TLR8) and DC-SIGN for replication in dendritic cells (DCs). HIV-1 activated the transcription factor NF-kappaB through TLR8 to initiate the transcription of integrated provirus by RNA polymerase II (RNAPII). However, DC-SIGN signaling was required for the generation of full-length viral transcripts. Binding of the HIV-1 envelope glycoprotein gp120 to DC-SIGN induced kinase Raf-1-dependent phosphorylation of the NF-kappaB subunit p65 at Ser276, which recruited the transcription-elongation factor pTEF-b to nascent transcripts. Transcription elongation and generation of full-length viral transcripts was dependent on pTEF-b-mediated phosphorylation of RNAPII at Ser2. Inhibition of either pathway abrogated replication and prevented HIV-1 transmission. Thus, HIV-1 subverts crucial components of the immune system for replication that might be targeted to prevent infection and dissemination.
- Publication
Nature immunology, 2010, Vol 11, Issue 5, p419
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1858