scholarly journals APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection

2006 ◽  
Vol 203 (13) ◽  
pp. 2887-2893 ◽  
Author(s):  
Marjorie Pion ◽  
Angela Granelli-Piperno ◽  
Bastien Mangeat ◽  
Romaine Stalder ◽  
Rafael Correa ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Messenger Rna ◽  
Cytidine Deaminase ◽  
Small Subset ◽  
Intrinsic Resistance ◽  
Susceptibility To Infection ◽  
Point Of Entry ◽  
Immature Dendritic Cells ◽  
Cytidine Deaminase Activity ◽  
Hiv 1

HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA–mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.

scholarly journals Binding of Human Immunodeficiency Virus Type 1 to Immature Dendritic Cells Can Occur Independently of DC-SIGN and Mannose Binding C-Type Lectin Receptors via a Cholesterol-Dependent Pathway

2003 ◽  
Vol 77 (23) ◽  
pp. 12865-12874 ◽  
Author(s):  
Suryaram Gummuluru ◽  
Mark Rogel ◽  
Leonidas Stamatatos ◽  
Michael Emerman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Virus Binding ◽  
Lectin Receptors ◽  
Virus Particles ◽  
Immature Dendritic Cells ◽  
Immunodeficiency Virus ◽  
Mannose Binding ◽  
Hiv 1

ABSTRACT Interactions of human immunodeficiency virus type 1 (HIV-1) with immature dendritic cells (DC) are believed to be multifactorial and involve binding to the CD4 antigen, DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), mannose binding C-type lectin receptors (MCLR), and heparan sulfate proteoglycans (HSPG). In this study we assessed the relative contributions of these previously defined virus attachment factors to HIV binding and accumulation in DC and the subsequent transfer of the bound virus particle to CD4+ T cells. Using competitive inhibitors of HIV-1 attachment to DC, we have identified the existence of DC-SIGN-, MCLR-, and HSPG-independent mechanism(s) of HIV attachment and internalization. Furthermore, virus particles bound by DC independently of CD4, DC-SIGN, MCLR, and HSPG are efficiently transmitted to T cells. Treatment of virus particles with the protease subtilisin or treatment of immature DC with trypsin significantly reduced virus binding, thus demonstrating the role of HIV envelope glycoprotein interactions with unidentified DC-surface factor(s). Finally, this DC-mediated virus binding and internalization are dependent on lipid rafts. We propose that pathways to HIV-1 attachment and uptake in DC exhibit functional redundancy; that is, they are made up of multiple independent activities that can, at least in part, compensate for one another.

scholarly journals Endogenously expressed HIV-1 nef down-regulates antigen-presenting molecules, not only class I MHC but also CD1a, in immature dendritic cells

Virology ◽  
2004 ◽  
Vol 326 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Eiji Shinya ◽  
Atsuko Owaki ◽  
Masumi Shimizu ◽  
Junko Takeuchi ◽  
Tetsuo Kawashima ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Class I ◽  
Class I Mhc ◽  
Immature Dendritic Cells ◽  
Antigen Presenting ◽  
Hiv 1

scholarly journals APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection

2006 ◽  
Vol 175 (6) ◽  
pp. i16-i16
Author(s):  
Marjorie Pion ◽  
Angela Granelli-Piperno ◽  
Bastien Mangeat ◽  
Romaine Stalder ◽  
Rafael Correa ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Intrinsic Resistance ◽  
Hiv 1

Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells

2004 ◽  
Author(s):  
Takuya Ohta ◽  
Hiroki Hori ◽  
Masahiro Ogawa ◽  
Masazumi Miyahara ◽  
Hajime Kawasaki ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Carcinoma Cells ◽  
Intrinsic Resistance ◽  
Cytidine Deaminase Activity

scholarly journals Extracellular ATP reduces HIV-1 transfer from immature dendritic cells to CD4+ T lymphocytes

Retrovirology ◽  
2008 ◽  
Vol 5 (1) ◽  
pp. 30 ◽  
Author(s):  
Corinne Barat ◽  
Caroline Gilbert ◽  
Michael Imbeault ◽  
Michel J Tremblay
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Extracellular Atp ◽  
Immature Dendritic Cells ◽  
Hiv 1

scholarly journals Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti–HIV-1 IgG without induction of maturation

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4466-4474 ◽  
Author(s):  
Vincent Holl ◽  
Maryse Peressin ◽  
Sylvie Schmidt ◽  
Thomas Decoville ◽  
Susan Zolla-Pazner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inhibitory Activity ◽  
Hiv Transmission ◽  
Autologous Blood ◽  
Target Cells ◽  
Hiv Replication ◽  
Cellular Targets ◽  
Immature Dendritic Cells ◽  
Hiv 1

AbstractDuring mucosal HIV transmission, immature dendritic cells (DCs) present in the mucosa are among the first cellular targets of the virus. Previous studies have analyzed the inhibition of HIV-1 transfer from human mature DCs to T lymphocytes by neutralizing IgG, but so far no in vitro data regarding the capacity of antibodies to inhibit HIV-1 infection of immature DCs have been reported. Here, we found an increased HIV-inhibitory activity of monoclonal IgG and purified polyclonal IgG when immature monocyte-derived dendritic cells (iMDDCs) were used as target cells instead of autologous blood lymphocytes. We showed that FcγRII is involved in the mechanism for inhibiting HIV-1 infection of iMDDCs by IgG, whereas no induction of maturation was detected at concentrations of IgG that result in a 90% reduction of HIV replication. After induction of FcγRI expression on iMDDCs by IFN-γ, an augmentation of the HIV-inhibitory activity of IgG, related to the expression of FcγRI, was observed. Taken together, our results demonstrate the participation of FcγRs in HIV-1 inhibition by IgG when iMDDCs are the targets. We propose that IgG is able to efficiently inhibit HIV-1 replication in iMDDCs and should be one of the components to be induced by vaccination.

scholarly journals Analysis of HIV-1-X4 Fusion with Immature Dendritic Cells Identifies a Specific Restriction that Is Independent of CXCR4 Levels

2007 ◽  
Vol 127 (2) ◽  
pp. 319-323 ◽  
Author(s):  
Marjorie Pion ◽  
Jean-Francois Arrighi ◽  
Jiyang Jiang ◽  
Christopher A. Lundquist ◽  
Oliver Hartley ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immature Dendritic Cells ◽  
Specific Restriction ◽  
Hiv 1

scholarly journals Uterine Epithelial Cell Regulation of DC-SIGN Expression Inhibits Transmitted/Founder HIV-1 Trans Infection by Immature Dendritic Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e14306 ◽  
Author(s):  
Daniel O. Ochiel ◽  
Christina Ochsenbauer ◽  
John C. Kappes ◽  
Mimi Ghosh ◽  
John V. Fahey ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Epithelial Cell ◽  
Cell Regulation ◽  
Uterine Epithelial Cell ◽  
Immature Dendritic Cells ◽  
Trans Infection ◽  
Hiv 1

Modulation of Dendritic Cell Chemotaxis by HIV-gp120.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1252-1252
Author(s):  
Anil P. Bailuguttu ◽  
Ramesh K. Ganju
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Specific Protein ◽  
Dependent Manner ◽  
Cell Immunity ◽  
Immature Dendritic Cells ◽  
Pre Treatment ◽  
Hiv Gp120 ◽  
Hiv 1 ◽  
Cell Chemotaxis

Abstract Dendritic cells are essential antigen-presenting cells involved in the induction of T cell immunity against pathogens, such as Human Immunodeficiency Virus (HIV)-1. During the early stages of HIV infection, immature dendritic cells (iDCs) are the first cellular targets of HIV-1. These HIV-infected iDCs cross mucosal surfaces and facilitate transmission of the virus to nearby CD4+ T cells. To date, the effect of HIV envelope proteins such as gp120 on dendritic cell chemotaxis has not been well characterized. Thus, we studied the effect of recombinant gp120 on the chemotaxis of mature DCs (mDCs) and immature DCs. Immature DCs have been shown to express the CC chemokine receptor, CCR5. In contrast, mature DCs down-regulate CCR5 but upregulate CXCR4 as well as exhibit enhanced chemotaxis towards CXCL12. In our study, we analyzed the effect of soluble gp120 on the chemotaxis of DCs. We have shown that pre-treatment of DCs with M-tropic gp120 significantly inhibited the CCR5-induced chemotaxis of iDCs, whereas pre-treatment of DCs with T-tropic gp120 inhibited the CXCL12-induced chemotaxis of mDCs. In addition, we found that M-tropic gp120 itself induced the chemotaxis of iDCs in a dose-dependent manner, while T-tropic gp120 did not show any effect on iDC chemotaxis. We next analyzed the signaling mechanisms involved in the modulation of iDC chemotaxis by M-tropic gp120 and found that M-tropic gp120 increased the phosphorylation of Src kinase, paxillin, Erk, and Akt in these cells. Moreover, M-tropic gp120 induced an increased expression of Lymphocyte Specific Protein-1 (LSP1), which has been reported to regulate the chemotaxis of various immune cells. Taken together, these results suggest that HIV-gp120 plays an important role in modulating the chemotaxis of mDCs and iDCs. This study may help to elucidate the mechanisms of immune response and contribute to the development of vaccines against HIV.

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