PMID- 21504576
OWN - NLM
STAT- MEDLINE
DCOM- 20110926
LR  - 20211020
IS  - 1742-4690 (Electronic)
IS  - 1742-4690 (Linking)
VI  - 8
DP  - 2011 Apr 19
TI  - Tetherin does not significantly restrict dendritic cell-mediated HIV-1 
      transmission and its expression is upregulated by newly synthesized HIV-1 Nef.
PG  - 26
LID - 10.1186/1742-4690-8-26 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are among the first cells to encounter HIV-1 
      and play important roles in viral transmission and pathogenesis. Immature DCs 
      allow productive HIV-1 replication and long-term viral dissemination. The 
      pro-inflammatory factor lipopolysaccharide (LPS) induces DC maturation and 
      enhances the efficiency of DC-mediated HIV-1 transmission. Type I interferon 
      (IFN) partially inhibits HIV-1 replication and cell-cell transmission in CD4+ T 
      cells and macrophages. Tetherin is a type I IFN-inducible restriction factor that 
      blocks HIV-1 release and modulates CD4+ T cell-mediated cell-to-cell transmission 
      of HIV-1. However, the role of type I IFN and tetherin in HIV-1 infection of DCs 
      and DC-mediated viral transmission remains unknown. RESULTS: We demonstrated that 
      IFN-alpha (IFNalpha)-induced mature DCs restricted HIV-1 replication and 
      trans-infection of CD4+ T cells. Tetherin expression in monocyte-derived immature 
      DCs was undetectable or very low. High levels of tetherin were transiently 
      expressed in LPS- and IFNalpha-induced mature DCs, while HIV-1 localized into 
      distinct patches in these DCs. Knockdown of induced tetherin in LPS- or 
      IFNalpha-matured DCs modestly enhanced HIV-1 transmission to CD4+ T cells, but had no 
      significant effect on wild-type HIV-1 replication in mature DCs. Intriguingly, we 
      found that HIV-1 replication in immature DCs induced significant tetherin 
      expression in a Nef-dependent manner. CONCLUSIONS: The restriction of HIV-1 
      replication and transmission in IFNalpha-induced mature DCs indicates a potent 
      anti-HIV-1 response; however, high levels of tetherin induced in mature DCs 
      cannot significantly restrict wild-type HIV-1 release and DC-mediated HIV-1 
      transmission. Nef-dependent tetherin induction in HIV-1-infected immature DCs 
      suggests an innate immune response of DCs to HIV-1 infection.
FAU - Coleman, Christopher M
AU  - Coleman CM
AD  - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio 
      State University, Columbus, OH 43210, USA.
FAU - Spearman, Paul
AU  - Spearman P
FAU - Wu, Li
AU  - Wu L
LA  - eng
GR  - R21 AI078762-03/AI/NIAID NIH HHS/United States
GR  - R21 AI078762/AI/NIAID NIH HHS/United States
GR  - AI 068493/AI/NIAID NIH HHS/United States
GR  - R01 AI068493-06/AI/NIAID NIH HHS/United States
GR  - AI 078762/AI/NIAID NIH HHS/United States
GR  - R01 AI068493/AI/NIAID NIH HHS/United States
GR  - R01 AI058828/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110419
PL  - England
TA  - Retrovirology
JT  - Retrovirology
JID - 101216893
RN  - 0 (Antigens, CD)
RN  - 0 (BST2 protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Interferon-alpha)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
RN  - 0 (nef protein, Human immunodeficiency virus 1)
SB  - IM
MH  - Antigens, CD/*immunology/*metabolism
MH  - CD4-Positive T-Lymphocytes/virology
MH  - Dendritic Cells/*immunology/*virology
MH  - GPI-Linked Proteins/antagonists & inhibitors/immunology/metabolism
MH  - Gene Knockdown Techniques
MH  - HIV-1/*growth & development/*immunology
MH  - Interferon-alpha/immunology
MH  - Lipopolysaccharides/immunology
MH  - nef Gene Products, Human Immunodeficiency Virus/immunology/metabolism
PMC - PMC3108291
EDAT- 2011/04/21 06:00
MHDA- 2011/09/29 06:00
PMCR- 2011/04/19
CRDT- 2011/04/21 06:00
PHST- 2011/01/23 00:00 [received]
PHST- 2011/04/19 00:00 [accepted]
PHST- 2011/04/21 06:00 [entrez]
PHST- 2011/04/21 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
PHST- 2011/04/19 00:00 [pmc-release]
AID - 1742-4690-8-26 [pii]
AID - 10.1186/1742-4690-8-26 [doi]
PST - epublish
SO  - Retrovirology. 2011 Apr 19;8:26. doi: 10.1186/1742-4690-8-26.