NDLI: SAMHD1 degradation enhances active suppression of dendritic cell maturation by HIV-1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gringhuis, Sonja I. Van Der Aar, Angelic M. G. Kootstra, Neeltje A. Setiawan, Laurentia C. Hertoghs, Nina Geijtenbeek, Teunis B. H.
Description	Author Affiliation: Hertoghs N ( Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands); van der Aar AM ( Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands); Setiawan LC ( Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands); Kootstra NA ( Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands); Gringhuis SI ( Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands); Geijtenbeek TB ( Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands)
Abstract	A hallmark of HIV-1 infection is the lack of sterilizing immunity. Dendritic cells (DCs) are crucial in the induction of immunity, and lack of DC activation might underlie the absence of an effective anti-HIV-1 response. We have investigated how HIV-1 infection affects maturation of DCs. Our data show that even though DCs are productively infected by HIV-1, infection does not induce DC maturation. HIV-1 infection actively suppresses DC maturation, as HIV-1 infection inhibited TLR-induced maturation of DCs and thereby decreased the immune stimulatory capacity of DCs. Interfering with SAMHD1 restriction further increased infection of DCs, but did not lead to DC maturation. Notably, higher infection observed with SAMHD1 depletion correlated with a stronger suppression of maturation. Furthermore, blocking reverse transcription rescued TLR-induced maturation. These data strongly indicate that HIV-1 replication does not trigger immune activation in DCs, but that HIV-1 escapes immune surveillance by actively suppressing DC maturation independent of SAMHD1. Elucidation of the mechanism of suppression can lead to promising targets for therapy or vaccine design.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dendritic Cells Immunology Metabolism Hiv Infections Hiv-1 Physiology Monomeric Gtp-binding Proteins Animals Cd4-positive T-lymphocytes Virology Cell Differentiation Cytology Immunomodulation Proteolysis Reverse Transcription Toll-like Receptors Viral Regulatory And Accessory Proteins Virus Replication Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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