scholarly journals STRL33, A Novel Chemokine Receptor–like Protein, Functions as a Fusion Cofactor for Both Macrophage-tropic and T Cell Line–tropic HIV-1

1997 ◽  
Vol 185 (11) ◽  
pp. 2015-2023 ◽  
Author(s):  
Fang Liao ◽  
Ghalib Alkhatib ◽  
Keith W.C. Peden ◽  
Geetika Sharma ◽  
Edward A. Berger ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Sequence Similarity ◽  
Jurkat Cells ◽  
Productive Infection ◽  
Lymphoid Tissues ◽  
Hiv 1

The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4+ cells can be explained, at least partly, by the selective use of G protein–coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor–like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line–tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.

scholarly journals CD4-Independent Infection of Two CD4−/CCR5−/CXCR4+ Pre-T-Cell Lines by Human and Simian Immunodeficiency Viruses

2000 ◽  
Vol 74 (14) ◽  
pp. 6689-6694 ◽  
Author(s):  
Alessandra Borsetti ◽  
Cristina Parolin ◽  
Barbara Ridolfi ◽  
Leonardo Sernicola ◽  
Andrea Geraci ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Chemokine Receptors ◽  
Immunodeficiency Virus ◽  
Cxcr4 Coreceptor ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT The infection of CD4-negative cells by variants of tissue culture-adapted human immunodeficiency virus type 1 (HIV-1) or HIV-2 strains has been shown to be mediated by the CXCR4 coreceptor. Here we show that two in vitro-established CD4−/CCR5−/CXCR4+ human pre-T-cell lines (A3 and A5) can be productively infected by wild-type laboratory-adapted T-cell-tropic HIV-1 and HIV-2 strains in a CD4-independent, CXCR4-dependent fashion. Despite the absence of CCR5 expression, A3 and A5 cells were susceptible to infection by the simian immunodeficiency viruses SIVmac239 and SIVmac316. Thus, at least in A3 and A5 cells, one or more of the chemokine receptors can efficiently support the entry of HIV and SIV isolates in the absence of CD4. These findings suggest that to infect cells of different compartments, HIV and SIV could have evolved in vivo to bypass CD4 and to interact directly with an alternative receptor.

scholarly journals Elucidating the basis for permissivity of the MT-4 T-cell line to replication of an HIV-1 mutant lacking the gp41 cytoplasmic tail

2020 ◽  
Author(s):  
Melissa V. Fernandez ◽  
Huxley K. Hoffman ◽  
Nairi Pezeshkian ◽  
Philip R. Tedbury ◽  
Schuyler B. van Engelenburg ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cytoplasmic Tail ◽  
Viral Transmission ◽  
Virus Particles ◽  
Cell Transmission ◽  
T Cell Lines ◽  
Hiv 1

AbstractHIV-1 encodes an envelope glycoprotein (Env) that contains a long cytoplasmic tail (CT) harboring trafficking motifs implicated in Env incorporation into virus particles and viral transmission. In most physiologically relevant cell types, the gp41 CT is required for HIV-1 replication, but in the MT-4 T-cell line the gp41 CT is not required for a spreading infection. To help elucidate the role of the gp41 CT in HIV-1 transmission, in this study we investigated the viral and cellular factors that contribute to the permissivity of MT-4 to gp41 CT truncation. We found that the kinetics of HIV-1 production are faster in MT-4 than in the other T-cell lines tested, but MT-4 express equivalent amounts of HIV-1 proteins on a per-cell basis relative to cells not permissive to CT truncation. MT-4 express higher levels of plasma-membrane-associated Env than non-permissive cells and Env internalization from the plasma membrane is slower compared to another T-cell line, SupT1. Paradoxically, despite the high levels of Env on the surface of MT-4, two-fold less Env is incorporated into virus particles in MT-4 compared to SupT1. Cell-to-cell transmission between co-cultured 293T and MT-4 is higher than in co-cultures of 293T with most other T-cell lines tested, indicating that MT-4 are highly susceptible to this mode of infection. These data help to clarify the long-standing question of how MT-4 cells overcome the requirement for the HIV-1 gp41 CT and support a role for gp41 CT-dependent trafficking in Env incorporation and cell-to-cell transmission in physiologically relevant cell lines.ImportanceThe HIV-1 Env cytoplasmic tail (CT) is required for efficient Env incorporation into nascent particles and viral transmission in primary CD4+ T cells. The MT-4 T-cell line has been reported to support multiple rounds of infection of HIV-1 encoding a gp41 CT truncation. Uncovering the underlying mechanism of MT-4 T-cell line permissivity to gp41 CT truncation would provide key insights into the role of the gp41 CT in HIV-1 transmission. This study reveals that multiple factors contribute to the unique ability of a gp41 CT truncation mutant to spread in cultures of MT-4 cells. The lack of a requirement for the gp41 CT in MT-4 is associated with the combined effects of rapid HIV-1 protein production, high levels of cell-surface Env expression, and increased susceptibility to cell-to-cell transmission compared to non-permissive cells.

scholarly journals Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1109-1116 ◽  
Author(s):  
Uta E. Höpken ◽  
Hans-Dieter Foss ◽  
Dagmar Meyer ◽  
Michael Hinz ◽  
Korinna Leder ◽  
...  
Keyword(s):  
Cell Lines ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Critical Role ◽  
Receptor Expression ◽  
Hodgkin Disease ◽  
Lymphoid Tissues ◽  
Neoplastic Cells ◽  
Chemokine Receptor Expression ◽  
Target Organs

Chemokines and chemokine receptors are key mediators for regulating cell traffic and positioning in both homeostatic and inflammatory conditions. It is also presumed that chemokines and their receptors are likely to play a critical role in the localization of malignant hematopoietic cells in their target organs. This study analyzed chemokine and chemokine receptor expression in several Hodgkin disease (HD)–derived cell lines and in HD tumors. All HD-derived cell lines expressed functional CCR7 and CXCR4 receptors. CCR7 up-regulation was mediated by constitutive NF-κB activity. Lymphoid tissues in HD revealed differential expression levels of CCR7, CXCR4, and CXCR5, depending on the distinct subtypes of HD. HD of the classical subtypes, predominantly located in the interfollicular zone, showed strong CCR7 and CXCR4 expression and moderate CXCR5 expression. In contrast, the nodular lymphocyte-predominant HD (NLP) subtype, regularly associated with follicular structures, exhibited no CCR7 reactivity but abundant CXCR4 staining. Their respective chemokine ligands showed marked expression by reactive cells within the tumors of classical HD and outside of the tumor nodules in NLPHD. Functionally, such differential chemokine receptor expression might contribute to specific localization and confinement of neoplastic cells within the target organs in the distinct HD entities.

scholarly journals Differentiating agents facilitate infection of myeloid leukemia cell lines by monocytotropic HIV-1 strains [published erratum appears in Blood 1991 Apr 1;77(7):1624]

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1980-1988 ◽  
Author(s):  
K Kitano ◽  
GC Baldwin ◽  
MA Raines ◽  
DW Golde
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Cell Lines ◽  
Virus Production ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Productive Infection ◽  
Differentiating Agents ◽  
Hiv 1

Abstract Monocytotropic human immunodeficiency virus type 1 (HIV-1) isolates from patients with acquired immunodeficiency syndrome (AIDS) infect mononuclear phagocytes as well as activated T cells, but do not usually infect immature human myeloid cell lines in vitro. The HL-60 promyelocytic/myeloblastic cell line and the promonocytic line, U937, were susceptible to productive infection by monocytotropic HIV-1 isolates (HIV-1JR-FL and HTLV-IIIBa-L) after treatment with retinoic acid, dimethyl sulfoxide, dibutyryl cAMP, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Virus production was only detected when these compounds were added before virus infection. Virus replication did not correlate with CD4 receptor expression because undifferentiated HL-60 cells express CD4 and the level of CD4 expression did not increase after differentiation in the presence of retinoic acid, 1,25(OH)2D3, or TPA. A mature monocytic cell line (THP-1) was capable of infection without pretreatment, and treatment with differentiating agents enhanced virus production. A chronically infected cell line (J-HL-60) was isolated after HIV-1JR-FL infection of HL-60 cells treated with retinoic acid. Virus production in this cell line was enhanced more than 10-fold after differentiation in the presence of 1,25(OH)2D3 or TPA. The majority of virus production by 1,25(OH)2D3-treated J-HL-60 cells was associated with the mature, adherent population. Molecular analysis of a cloned line of J-HL-60 showed integration of a single DNA provirus. These results suggest that cellular factors associated with precursor cell differentiation along the myelomonocytic pathway are required for optimal replication of monocytotropic HIV-1 strains in vitro.

scholarly journals Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 213-219
Author(s):  
SM Hsu ◽  
MD Pescovitz ◽  
PL Hsu
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Cell Lymphoma ◽  
Hodgkin’S Disease ◽  
Lymphoid Tissues ◽  
Malignant Histiocytosis ◽  
Histiocytic Lymphoma

Three murine monoclonal antibodies, named 2H9, 1E9 and 1A2, were produced after immunization of BALB/c mice with cells of the SU-DHL-1 cell line from a true histiocytic lymphoma. In frozen sections from various lymphomas, 2H9 and 1A2 selectively stained the cell membranes of neoplastic cells in true histiocytic lymphoma and Hodgkin's disease. Antibody 1E9 stained the nuclear membranes of the tumor cells in true histiocytic lymphoma and malignant histiocytosis. No staining was seen in 56 cases of B and T cell lymphoma. Several tissue culture cell lines, including T cell acute lymphoblastic leukemia and pre-B cell lines, were not stained. With 2H9, however, a positive reaction was noted for two Epstein-Barr virus (EBV)-positive African Burkitt's lymphoma cell lines (Daudi and P3HRI), one human T cell lymphoma/leukemia-virus-positive cell line (HUT 102), and one EBV- transformed normal B lymphoblastoid cell line (RPMI 8057). In normal lymphoid tissues, 2H9 and 1E9 reacted with the nuclear membranes of histiocytes and interdigitating reticulum cells, whereas 1A2 stained only rare cells of an unknown type. All three antibodies failed to react with B or T cells in frozen tissue sections of normal lymphoid tissues. The use of these three antibodies should facilitate the diagnosis of histiocyte and interdigitating reticulum (IR) cell-related neoplasms, namely, true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. True histiocytic lymphoma and Hodgkin's disease exhibit similar reactivities with these three and with two other monoclonal antibodies (HeFi-1 and Tac), suggesting that these two types of lymphoma are related. In contrast, malignant histiocytosis was negative for 2H9, 1A2, Tac, and HeFi-1. The difference in the phenotypic expression of true histiocytic lymphoma and malignant histiocytosis indicates that they are two different disease entities.

scholarly journals c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5738
Author(s):  
Chung Hyo Kang ◽  
Yeongrin Kim ◽  
Da Yeon Lee ◽  
Sang Un Choi ◽  
Heung Kyoung Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Jurkat Cells ◽  
Car T Cells ◽  
Car T

Chimeric antigen receptor (CAR) technology has been highlighted in recent years as a new therapeutic approach for cancer treatment. Although the impressive efficacy of CAR-based T cell adoptive immunotherapy has been observed in hematologic cancers, limited effect has been reported on solid tumors. Approximately 20% of gastric cancer (GC) patients exhibit a high expression of c-Met. We have generated an anti c-Met CAR construct that is composed of a single-chain variable fragment (scFv) of c-Met antibody and signaling domains consisting of CD28 and CD3ζ. To test the CAR construct, we used two cell lines: the Jurkat and KHYG-1 cell lines. These are convenient cell lines, compared to primary T cells, to culture and to test CAR constructs. We transduced CAR constructs into Jurkat cells by electroporation. c-Met CAR Jurkat cells secreted interleukin-2 (IL-2) only when incubated with c-Met positive GC cells. To confirm the lytic function of CAR, the CAR construct was transduced into KHYG-1, a NK/T cell line, using lentiviral particles. c-Met CAR KHYG-1 showed cytotoxic effect on c-Met positive GC cells, while c-Met negative GC cell lines were not eradicated by c-Met CAR KHYG-1. Based on these data, we created c-Met CAR T cells from primary T cells, which showed high IL-2 and IFN-γ secretion when incubated with the c-Met positive cancer cell line. In an in vivo xenograft assay with NSG bearing MKN-45, a c-Met positive GC cell line, c-Met CAR T cells effectively inhibited the tumor growth of MKN-45. Our results show that the c-Met CAR T cell therapy can be effective on GC.

CD45RO regulates the HIV-1 gp120-mediated apoptosis of T cells by activating Lck

2018 ◽  
Vol 399 (6) ◽  
pp. 583-591
Author(s):  
Kelei Li ◽  
Zhe Cong ◽  
Zhuoying Peng ◽  
Ting Chen ◽  
Jing Xue ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Tyrosine Phosphatase ◽  
Extracellular Domain ◽  
Jurkat Cells ◽  
Transfected Cells ◽  
Induced Apoptosis ◽  
Hiv 1

Abstract CD45 has been reported to regulate the HIV-1 gp120-induced apoptosis of Jurkat cells. Here, we demonstrate that the extracellular domain of CD45 plays an important role in this function. We observed that CD45RO-transfected cells, but not cells transfected with other CD45 isoforms, underwent significant apoptosis induced by gp120. However, a CD45RA-transfected cell line treated with an O-glycan inhibitor was able to undergo apoptosis. The role of the extracellular domain of CD45 was further confirmed using CD45 isoform-transfected cell lines by analyzing the phosphorylation of Lck, which is a direct substrate of CD45 tyrosine phosphatase, and by using an Lck inhibitor. These results suggest that CD45RO modulates HIV-1 gp120-induced apoptosis by regulating the activity of Lck.

scholarly journals Elucidating the Basis for Permissivity of the MT-4 T-Cell Line to Replication of an HIV-1 Mutant Lacking the gp41 Cytoplasmic Tail

2020 ◽  
Vol 94 (23) ◽  
Author(s):  
Melissa V. Fernandez ◽  
Huxley K. Hoffman ◽  
Nairi Pezeshkian ◽  
Philip R. Tedbury ◽  
Schuyler B. van Engelenburg ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cytoplasmic Tail ◽  
Viral Transmission ◽  
Virus Particles ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT HIV-1 encodes an envelope glycoprotein (Env) that contains a long cytoplasmic tail (CT) harboring trafficking motifs implicated in Env incorporation into virus particles and viral transmission. In most physiologically relevant cell types, the gp41 CT is required for HIV-1 replication, but in the MT-4 T-cell line the gp41 CT is not required for a spreading infection. To help elucidate the role of the gp41 CT in HIV-1 transmission, in this study, we investigated the viral and cellular factors that contribute to the permissivity of MT-4 cells to gp41 CT truncation. We found that the kinetics of HIV-1 production and virus release are faster in MT-4 than in the other T-cell lines tested, but MT-4 cells express equivalent amounts of HIV-1 proteins on a per-cell basis relative to cells not permissive to CT truncation. MT-4 cells express higher levels of plasma-membrane-associated Env than nonpermissive cells, and Env internalization from the plasma membrane is less efficient than that from another T-cell line, SupT1. Paradoxically, despite the high levels of Env on the surface of MT-4 cells, 2-fold less Env is incorporated into virus particles produced from MT-4 than SupT1 cells. Contact-dependent transmission between cocultured 293T and MT-4 cells is higher than in cocultures of 293T with most other T-cell lines tested, indicating that MT-4 cells are highly susceptible to cell-to-cell infection. These data help to clarify the long-standing question of how MT-4 cells overcome the requirement for the HIV-1 gp41 CT and support a role for gp41 CT-dependent trafficking in Env incorporation and cell-to-cell transmission in physiologically relevant cell lines. IMPORTANCE The HIV-1 Env cytoplasmic tail (CT) is required for efficient Env incorporation into nascent particles and viral transmission in primary CD4+ T cells. The MT-4 T-cell line has been reported to support multiple rounds of infection of HIV-1 encoding a gp41 CT truncation. Uncovering the underlying mechanism of MT-4 T-cell line permissivity to gp41 CT truncation would provide key insights into the role of the gp41 CT in HIV-1 transmission. This study reveals that multiple factors contribute to the unique ability of a gp41 CT truncation mutant to spread in cultures of MT-4 cells. The lack of a requirement for the gp41 CT in MT-4 cells is associated with the combined effects of rapid HIV-1 protein production, high levels of cell-surface Env expression, and increased susceptibility to cell-to-cell transmission compared to nonpermissive cells.

scholarly journals A Small Molecule CXCR4 Inhibitor that Blocks T Cell Line–tropic HIV-1 Infection

1997 ◽  
Vol 186 (8) ◽  
pp. 1389-1393 ◽  
Author(s):  
Tsutomu Murakami ◽  
Toshihiro Nakajima ◽  
Yoshio Koyanagi ◽  
Kazunobu Tachibana ◽  
Nobutaka Fujii ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Growth ◽  
B Cell ◽  
Cell Line ◽  
Small Molecule ◽  
Chemokine Receptor ◽  
Mononuclear Cells ◽  
Target Cells ◽  
Stimulating Factor ◽  
Hiv 1

Several members of the chemokine receptor family have been shown to function in association with CD4 to permit human immunodeficiency virus type 1 (HIV-1) entry and infection. The CXC chemokine receptor CXCR4/fusin is a receptor for pre–B cell growth stimulating factor (PBSF)/stromal cell–derived factor 1 (SDF-1) and serves as a coreceptor for the entry of T cell line–tropic HIV-1 strains. Thus, the development of CXCR4 antagonists or agonists may be useful in the treatment of HIV-1 infection. T22 ([Tyr5,12,Lys7]-polyphemusin II) is a synthesized peptide that consists of 18 amino acid residues and an analogue of polyphemusin II isolated from the hemocyte debris of American horseshoe crabs (Limulus polyphemus). T22 was found to specifically inhibit the ability of T cell line–tropic HIV-1 to induce cell fusion and infect the cell lines transfected with CXCR4 and CD4 or peripheral blood mononuclear cells. In addition, T22 inhibited Ca2+ mobilization induced by pre–B cell growth stimulating factor (PBSF)/SDF-1 stimulation through CXCR4. Thus, T22 is a small molecule CXCR4 inhibitor that blocks T cell line–tropic HIV-1 entry into target cells.

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