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 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 Costimulation of Naive CD8+ Lymphocytes Induces CD4 Expression and Allows Human Immunodeficiency Virus Type 1 Infection

1998 ◽  
Vol 72 (11) ◽  
pp. 9054-9060 ◽  
Author(s):  
Scott G. Kitchen ◽  
Yael D. Korin ◽  
Michael D. Roth ◽  
Alan Landay ◽  
Jerome A. Zack
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Rapid Disease Progression ◽  
Cd8 Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection requires cell surface expression of CD4. Costimulation of CD8+/CD4− T lymphocytes by anti-CD3 and anti-CD28 antibodies or by allogeneic dendritic cells induced expression of CD4 and rendered these CD8 cells susceptible to HIV-1 infection. Naive CD45RA+ cells responded with greater expression of CD4 than did CD45RO+ cells. CD8+lymphocytes derived from fetal or newborn sources exhibited a greater tendency to express CD4, consistent with their naive states. This mechanism of infection suggests HIV-induced perturbation of the CD8 arm of the immune response and could explain the generally rapid disease progression seen in HIV-infected children.

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 DC-SIGN Interactions with Human Immunodeficiency Virus Type 1 and 2 and Simian Immunodeficiency Virus

2001 ◽  
Vol 75 (10) ◽  
pp. 4664-4672 ◽  
Author(s):  
Stefan Pöhlmann ◽  
Frédéric Baribaud ◽  
Benhur Lee ◽  
George J. Leslie ◽  
Melissa D. Sanchez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Lectin Binding ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Virus Binding ◽  
Expression Levels ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Dendritic cells (DCs) efficiently bind and transmit human immunodeficiency virus (HIV) to cocultured T cells and so may play an important role in HIV transmission. DC-SIGN, a novel C-type lectin that is expressed in DCs, has recently been shown to bind R5 HIV type 1 (HIV-1) strains and a laboratory-adapted X4 strain. To characterize the interaction of DC-SIGN with primate lentiviruses, we investigated the structural determinants of DC-SIGN required for virus binding and transmission to permissive cells. We constructed a panel of DC-SIGN mutants and established conditions which allowed comparable cell surface expression of all mutants. We found that R5, X4, and R5X4 HIV-1 isolates as well as simian immunodeficiency and HIV-2 strains bound to DC-SIGN and could be transmitted to CD4/coreceptor-positive cell types. DC-SIGN contains a single N-linked carbohydrate chain that is important for efficient cell surface expression but is not required for DC-SIGN-mediated virus binding and transmission. In contrast, C-terminal deletions removing either the lectin binding domain or the repeat region abrogated DC-SIGN function. Trypsin-EDTA treatment inhibited DC-SIGN mediated infection, indicating that virus was maintained at the surface of the DC-SIGN-expressing cells used in this study. Finally, quantitative fluorescence-activated cell sorting analysis of AU1-tagged DC-SIGN revealed that the efficiency of virus transmission was strongly affected by variations in DC-SIGN expression levels. Thus, variations in DC-SIGN expression levels on DCs could greatly affect the susceptibility of human individuals to HIV infection.

scholarly journals Targeting of the Human Immunodeficiency Virus Type 1 Envelope to the trans-Golgi Network through Binding to TIP47 Is Required for Env Incorporation into Virions and Infectivity

2003 ◽  
Vol 77 (12) ◽  
pp. 6931-6945 ◽  
Author(s):  
Guillaume Blot ◽  
Katy Janvier ◽  
Sophie Le Panse ◽  
Richard Benarous ◽  
Clarisse Berlioz-Torrent
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Retrograde Transport ◽  
Cytoplasmic Domain ◽  
Immunodeficiency Virus ◽  
Golgi Network ◽  
Hiv 1

ABSTRACT Here, we report that human immunodeficiency virus type 1 (HIV-1) Env glycoprotein is located mainly in the trans-Golgi network (TGN) due to determinants present in the cytoplasmic domain of the transmembrane gp41 glycoprotein (TMgp41). Internalization assays demonstrated that Env present at the cell surface returns to the TGN. We found that the cytoplasmic domain of TMgp41 binds to TIP47, a protein required for the transport of mannose-6-phosphate receptors from endosomes to the TGN. Overexpression of a mutant of TIP47 affected the transport of Env from endosomes to the TGN. Retrograde transport of Env to the TGN requires a Y802W803 diaromatic motif present in the TMgp41 cytoplasmic domain. Mutation of this motif abolished both targeting to the TGN as well as interaction with TIP47. These data support the view that binding of TIP47 to HIV-1 Env facilitates its delivery to the TGN. Lastly, we show that virus mutated in the Y802W803 motif is poorly infectious and presents a defect in Env incorporation, supporting a model in which retrograde transport of Env is implicated in the optimization of fully infectious HIV-1 production.

scholarly journals Hemofiltrate CC Chemokine 1[9-74] Causes Effective Internalization of CCR5 and Is a Potent Inhibitor of R5-Tropic Human Immunodeficiency Virus Type 1 Strains in Primary T Cells and Macrophages

2002 ◽  
Vol 46 (4) ◽  
pp. 982-990 ◽  
Author(s):  
Jan Münch ◽  
Ludger Ständker ◽  
Stefan Pöhlmann ◽  
Frédéric Baribaud ◽  
Armin Papkalla ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Proteolytic Processing ◽  
Cell Surface Expression ◽  
Cc Chemokine ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Proteolytic processing of the abundant plasmatic human CC chemokine 1 (HCC-1) generates a truncated form, HCC-1[9-74], which is a potent agonist of CCR1, CCR3, and CCR5; promotes calcium influx and chemotaxis of T lymphoblasts, monocytes, and eosinophils; and inhibits infection by CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates. In the present study we demonstrate that HCC-1[9-74] interacts with the second external loop of CCR5 and inhibits replication of CCR5-tropic HIV-1 strains in both primary T cells and monocyte-derived macrophages. Low concentrations of the chemokine, however, frequently enhanced the replication of CCR5-tropic HIV-1 isolates but not the replication of X4-tropic HIV-1 isolates. Only HCC-1[9-74] and HCC-1[10-74], but not other HCC-1 length variants, displayed potent anti-HIV-1 activities. Fluorescence-activated cell sorter analysis revealed that HCC-1[9-74] caused up to 75% down-regulation of CCR5 cell surface expression, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) achieved a reduction of only about 40%. Studies performed with green fluorescent protein-tagged CCR5 confirmed that both HCC-1[9-74] and RANTES, but not full-length HCC-1, mediated specific internalization of the CCR5 HIV-1 entry cofactor. Our results demonstrate that the interaction with HCC-1[9-74] causes effective intracellular sequestration of CCR5, but they also indicate that the effect of HCC-1[9-74] on viral replication is subject to marked cell donor- and HIV-1 isolate-dependent variations.

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