scholarly journals The Transmembrane Protein of HIV-1 Primary Isolates Modulates Cell Surface Expression of Their Envelope Glycoproteins

Virology ◽  
2001 ◽  
Vol 290 (1) ◽  
pp. 136-142
Author(s):  
Sarah Lebigot ◽  
Philippe Roingeard ◽  
Gilles Thibault ◽  
Franck Lemiale ◽  
Bernard Verrier ◽  
...  
Keyword(s):  
Cell Surface ◽  
Transmembrane Protein ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Envelope Glycoproteins ◽  
Hiv 1

scholarly journals Interactions of the Cytoplasmic Domains of Human and Simian Retroviral Transmembrane Proteins with Components of the Clathrin Adaptor Complexes Modulate Intracellular and Cell Surface Expression of Envelope Glycoproteins

1999 ◽  
Vol 73 (2) ◽  
pp. 1350-1361 ◽  
Author(s):  
Clarisse Berlioz-Torrent ◽  
Barbara L. Shacklett ◽  
Lars Erdtmann ◽  
Lelia Delamarre ◽  
Isabelle Bouchaert ◽  
...  
Keyword(s):  
Cell Surface ◽  
Virus Type ◽  
Surface Expression ◽  
Cytoplasmic Domain ◽  
Major Determinant ◽  
Cell Surface Expression ◽  
Envelope Glycoproteins ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXØ, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-TM-CD chimeras to investigate the role of the Tyr-based motif of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and human T-leukemia virus type 1 (HTLV-1) TM-CDs in the cell surface expression of the envelope glycoprotein. Flow cytometry and confocal microscopy studies showed that this motif is a major determinant of the cell surface expression of the CD8-HTLV chimera. The YXXØ motif also plays a key role in subcellular distribution of the envelope of lentiviruses HIV-1 and SIV. However, these viruses, which encode TM proteins with a long cytoplasmic domain, have additional determinants distal to the YXXØ motif that participate in regulating cell surface expression. We have also used the yeast two-hybrid system and in vitro binding assays to demonstrate that all three retroviral YXXØ motifs interact with the μ1 and μ2 subunits of AP complexes and that the C-terminal regions of HIV-1 and SIV TM proteins interact with the β2 adaptin subunit. The TM-CDs of HTLV-1, HIV-1, and SIV also interact with the whole AP complexes. These results clearly demonstrate that the cell surface expression of retroviral envelope glycoproteins is governed by interactions with adaptor complexes. The YXXØ-based signal is the major determinant of this interaction for the HTLV-1 TM, which contains a short cytoplasmic domain, whereas the lentiviruses HIV-1 and SIV have additional determinants distal to this signal that are also involved.

scholarly journals Poxvirus Complement Control Proteins Are Expressed on the Cell Surface through an Intermolecular Disulfide Bridge with the Viral A56 Protein

2010 ◽  
Vol 84 (21) ◽  
pp. 11245-11254 ◽  
Author(s):  
Brian C. DeHaven ◽  
Natasha M. Girgis ◽  
Yuhong Xiao ◽  
Paul N. Hudson ◽  
Victoria A. Olson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Transmembrane Protein ◽  
Surface Expression ◽  
Disulfide Bridge ◽  
Eukaryotic Cell ◽  
Cell Surface Expression ◽  
Complement Control Proteins ◽  
Express Cell ◽  
Infected Cells

ABSTRACT The vaccinia virus (VACV) complement control protein (VCP) is an immunomodulatory protein that is both secreted from and expressed on the surface of infected cells. Surface expression of VCP occurs though an interaction with the viral transmembrane protein A56 and is dependent on a free N-terminal cysteine of VCP. Although A56 and VCP have been shown to interact in infected cells, the mechanism remains unclear. To investigate if A56 is sufficient for surface expression, we transiently expressed VCP and A56 in eukaryotic cell lines and found that they interact on the cell surface in the absence of other viral proteins. Since A56 contains three extracellular cysteines, we hypothesized that one of the cysteines may be unpaired and could therefore form a disulfide bridge with VCP. To test this, we generated a series of A56 mutants in which each cysteine was mutated to a serine, and we found that mutation of cysteine 162 abrogated VCP cell surface expression. We also tested the ability of other poxvirus complement control proteins to bind to VACV A56. While the smallpox homolog of VCP is able to bind VACV A56, the ectromelia virus (ECTV) VCP homolog is only able to bind the ECTV homolog of A56, indicating that these proteins may have coevolved. Surface expression of poxvirus complement control proteins may have important implications in viral pathogenesis, as a virus that does not express cell surface VCP is attenuated in vivo. This suggests that surface expression of VCP may contribute to poxvirus pathogenesis.

scholarly journals HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell–mediated killing

Blood ◽  
2010 ◽  
Vol 115 (7) ◽  
pp. 1354-1363 ◽  
Author(s):  
Jonathan Richard ◽  
Sardar Sindhu ◽  
Tram N. Q. Pham ◽  
Jean-Philippe Belzile ◽  
Éric A. Cohen
Keyword(s):  
Dna Damage ◽  
Cell Surface ◽  
Nk Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Target Cells ◽  
Nkg2d Ligands ◽  
Infected Cells ◽  
Nkg2d Receptor ◽  
Hiv 1

AbstractHIV up-regulates cell-surface expression of specific ligands for the activating NKG2D receptor, including ULBP-1, -2, and -3, but not MICA or MICB, in infected cells both in vitro and in vivo. However, the viral factor(s) involved in NKG2D ligand expression still remains undefined. HIV-1 Vpr activates the DNA damage/stress-sensing ATR kinase and promotes G2 cell-cycle arrest, conditions known to up-regulate NKG2D ligands. We report here that HIV-1 selectively induces cell-surface expression of ULBP-2 in primary CD4+ T lymphocytes by a process that is Vpr dependent. Importantly, Vpr enhanced the susceptibility of HIV-1–infected cells to NK cell–mediated killing. Strikingly, Vpr alone was sufficient to up-regulate expression of all NKG2D ligands and thus promoted efficient NKG2D-dependent NK cell–mediated killing. Delivery of virion-associated Vpr via defective HIV-1 particles induced analogous biologic effects in noninfected target cells, suggesting that Vpr may act similarly beyond infected cells. All these activities relied on Vpr ability to activate the ATR-mediated DNA damage/stress checkpoint. Overall, these results indicate that Vpr is a key determinant responsible for HIV-1–induced up-regulation of NKG2D ligands and further suggest an immunomodulatory role for Vpr that may not only contribute to HIV-1–induced CD4+ T-lymphocyte depletion but may also take part in HIV-1–induced NK-cell dysfunction.

scholarly journals Effect of Calcium-Modulating Cyclophilin Ligand on Human Immunodeficiency Virus Type 1 Particle Release and Cell Surface Expression of Tetherin

2009 ◽  
Vol 83 (24) ◽  
pp. 13032-13036 ◽  
Author(s):  
Mariana G. Bego ◽  
Mathieu Dubé ◽  
Johanne Mercier ◽  
Éric A. Cohen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Particle Release ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpu enhances virus particle release by counteracting a host factor that retains virions at the surfaces of infected cells. It was recently demonstrated that cellular protein BST-2/CD317/Tetherin restricts HIV-1 release in a Vpu-dependent manner. Calcium-modulating cyclophilin ligand (CAML) was also proposed to be involved in this process. We investigated whether CAML is involved in cell surface expression of Tetherin. Here, we show that CAML overexpression in permissive Cos-7 cells or CAML depletion in restrictive HeLa cells has no effect on HIV-1 release or on Tetherin surface expression, indicating that CAML is not required for Tetherin-mediated restriction of HIV-1 release.

scholarly journals Aminooxypentane-RANTES Induces CCR5 Internalization but Inhibits Recycling: A Novel Inhibitory Mechanism of HIV Infectivity

1998 ◽  
Vol 187 (8) ◽  
pp. 1215-1224 ◽  
Author(s):  
Matthias Mack ◽  
Bruno Luckow ◽  
Peter J. Nelson ◽  
Josef Cihak ◽  
Graham Simmons ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Chinese Hamster ◽  
Surface Expression ◽  
Receptor Internalization ◽  
Cell Surface Expression ◽  
Macrophage Infection ◽  
Potent Inhibition ◽  
Hiv 1

CCR5, a chemokine receptor expressed on T cells and macrophages, is the principal coreceptor for M-tropic HIV-1 strains. Recently, we described an NH2-terminal modification of the CCR5 ligand regulated on activation, normal T cell expressed and secreted (RANTES), aminooxypentane-RANTES (AOP-RANTES), that showed potent inhibition of macrophage infection by HIV-1 under conditions where RANTES was barely effective. To investigate the mechanism of AOP-RANTES inhibition of HIV infectivity we examined the surface expression of CCR5 using a monoclonal anti-CCR5 antibody, MC-1. We demonstrate that AOP-RANTES rapidly caused >90% decrease in cell surface expression of CCR5 on lymphocytes, monocytes/ macrophages, and CCR5 transfected Chinese hamster ovary (CHO) cells. RANTES also caused a loss of cell surface CCR5, although its effect was less than with AOP-RANTES. Significantly, AOP-RANTES inhibited recycling of internalized CCR5 to the cell surface, whereas RANTES did not. When peripheral blood mononuclear cells are cultured for prolonged periods of time in the presence of RANTES, CCR5 expression is comparable to that seen on cells treated with control medium, whereas there is no CCR5 surface expression on cells cultured in the presence of AOP-RANTES. Immunofluorescence indicated that both AOP-RANTES and RANTES induced downmodulation of cell surface CCR5, and that the receptor was redistributed into endocytic organelles containing the transferrin receptor. When RANTES was removed, the internalized receptor was recycled to the cell surface; however, the receptor internalized in the presence of AOP-RANTES was retained in endosomes. Using human osteosarcoma (GHOST) 34/CCR5 cells, the potency of AOP-RANTES and RANTES to inhibit infection by the M-tropic HIV-1 strain, SF 162, correlated with the degree of downregulation of CCR5 induced by the two chemokines. These differences between AOP-RANTES and RANTES in their effect on receptor downregulation and recycling suggest a mechanism for the potent inhibition of HIV infection by AOP-RANTES. Moreover, these results support the notion that receptor internalization and inhibition of receptor recycling present new targets for therapeutic agents to prevent HIV infection.

scholarly journals Nef-Induced CD4 Endocytosis in Human Immunodeficiency Virus Type 1 Host Cells: Role of p56lck Kinase

2009 ◽  
Vol 83 (14) ◽  
pp. 7117-7128 ◽  
Author(s):  
Nadine Laguette ◽  
Christelle Brégnard ◽  
Jérôme Bouchet ◽  
Alexandre Benmerah ◽  
Serge Benichou ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Surface Expression ◽  
Lymphoid Cells ◽  
Cell Surface Expression ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Internalization Rate ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Nef interferes with the endocytic machinery to modulate the cell surface expression of CD4. However, the basal trafficking of CD4 is governed by different rules in the target cells of HIV-1: whereas CD4 is rapidly internalized from the cell surface in myeloid cells, CD4 is stabilized at the plasma membrane through its interaction with the p56 lck kinase in lymphoid cells. In this study, we showed that Nef was able to downregulate CD4 in both lymphoid and myeloid cell lines but that an increase in the internalization rate of CD4 could be observed only in lymphoid cells. Expression of p56 lck in nonlymphoid CD4-expressing cells restores the ability of Nef in order to increase the internalization rate of CD4. Concurrent with this observation, the expression of a p56 lck -binding-deficient mutant of CD4 in lymphoid cells abrogates the Nef-induced acceleration of CD4 internalization. We also show that the expression of Nef causes a decrease in the association of p56 lck with cell surface-expressed CD4. Regardless of the presence of p56 lck , the downregulation of CD4 by Nef was followed by CD4 degradation. Our results imply that Nef uses distinct mechanisms to downregulate the cell surface expression levels of CD4 in either lymphoid or myeloid target cells of HIV-1.

scholarly journals Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1

2004 ◽  
Vol 85 (7) ◽  
pp. 1945-1954 ◽  
Author(s):  
Muriel Derrien ◽  
Nathalie Pizzato ◽  
Guillermina Dolcini ◽  
Elisabeth Menu ◽  
Gérard Chaouat ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Glioma Cells ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Immunodeficiency Virus ◽  
Immune Defences ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1 ◽  
Major Histocompatibility Class I

Human immunodeficiency virus 1 (HIV-1) downregulates cell surface expression of HLA-A and HLA-B but not HLA-C or HLA-E to ultimately escape immune defences. Here, it is shown that cell surface expression of the non-classical HLA-G1 is also downregulated by HIV-1, by using co-transfection experiments and infection with cell-free HIV-1 of HLA-G1-expressing U87 glioma cells or macrophages in primary culture. Moreover, co-transfection experiments using proviruses deleted in either nef or vpu or plasmids encoding HIV-1 Nef and Vpu mixed together with a HLA-G1-expressing construct demonstrated that HLA-G1 downregulation is Nef-independent and Vpu-dependent, contrasting with the Nef- and Vpu-dependent HLA-A2 downregulation. Together, these results show that the decrease of HLA-A2 and HLA-G1 caused by HIV-1 occurs through distinct mechanisms.

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