PMID- 25825449
OWN - NLM
STAT- MEDLINE
DCOM- 20150630
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 194
IP  - 9
DP  - 2015 May 1
TI  - SAMHD1 degradation enhances active suppression of dendritic cell maturation by 
      HIV-1.
PG  - 4431-7
LID - 10.4049/jimmunol.1403016 [doi]
AB  - 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.
CI  - Copyright (c) 2015 by The American Association of Immunologists, Inc.
FAU - Hertoghs, Nina
AU  - Hertoghs N
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, 1105 AZ Amsterdam, the Netherlands; and.
FAU - van der Aar, Angelic M G
AU  - van der Aar AM
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, 1105 AZ Amsterdam, the Netherlands; and.
FAU - Setiawan, Laurentia C
AU  - Setiawan LC
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, 1105 AZ Amsterdam, the Netherlands; and Laboratory of Viral Immune 
      Pathogenesis, Department of Experimental Immunology, Center for Infection and 
      Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
FAU - Kootstra, Neeltje A
AU  - Kootstra NA
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, 1105 AZ Amsterdam, the Netherlands; and Laboratory of Viral Immune 
      Pathogenesis, Department of Experimental Immunology, Center for Infection and 
      Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
FAU - Gringhuis, Sonja I
AU  - Gringhuis SI
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, 1105 AZ Amsterdam, the Netherlands; and.
FAU - Geijtenbeek, Teunis B H
AU  - Geijtenbeek TB
AD  - Department of Experimental Immunology, Academic Medical Center, University of 
      Amsterdam, 1105 AZ Amsterdam, the Netherlands; and t.b.geijtenbeek@amc.uva.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150330
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Toll-Like Receptors)
RN  - 0 (VPX protein, Simian immunodeficiency virus)
RN  - 0 (Viral Regulatory and Accessory Proteins)
RN  - EC 3.1.5.- (SAM Domain and HD Domain-Containing Protein 1)
RN  - EC 3.1.5.- (SAMHD1 protein, human)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism/virology
MH  - Cell Differentiation
MH  - Dendritic Cells/cytology/*immunology/*metabolism/virology
MH  - HIV Infections/*immunology/*metabolism
MH  - HIV-1/*physiology
MH  - Humans
MH  - Immunomodulation
MH  - Monomeric GTP-Binding Proteins/*metabolism
MH  - Proteolysis
MH  - Reverse Transcription
MH  - SAM Domain and HD Domain-Containing Protein 1
MH  - Toll-Like Receptors/metabolism
MH  - Viral Regulatory and Accessory Proteins/metabolism
MH  - Virus Replication
EDAT- 2015/04/01 06:00
MHDA- 2015/07/01 06:00
CRDT- 2015/04/01 06:00
PHST- 2014/12/02 00:00 [received]
PHST- 2015/02/26 00:00 [accepted]
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2015/07/01 06:00 [medline]
AID - jimmunol.1403016 [pii]
AID - 10.4049/jimmunol.1403016 [doi]
PST - ppublish
SO  - J Immunol. 2015 May 1;194(9):4431-7. doi: 10.4049/jimmunol.1403016. Epub 2015 Mar 
      30.