The role of CD38 in HIV infection

AbstractThe widely-expressed molecule CD38 is a single-stranded type II transmembrane glycoprotein that is mainly involved in regulating the differentiation and activation state of the cell. CD38 has broad and complex functions, including enzymatic activity, intercellular signal transduction, cell activation, cytokine production, receptor function and adhesion activity, and it plays an important role in the physiological and pathological processes of many diseases. Many studies have shown that CD38 is related to the occurrence and development of HIV infection, and CD38 may regulate its progression through different mechanisms. Therefore, investigating the role of CD38 in HIV infection and the potential signaling pathways that are involved may provide a new perspective on potential treatments for HIV infection. In the present review, the current understanding of the roles CD38 plays in HIV infection are summarized. In addition, the specific role of CD38 in the process of HIV infection of human CD4+ T lymphocytes is also discussed.

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CD38 as an immunomodulator in cancer

Future Oncology ◽

10.2217/fon-2020-0401 ◽

2020 ◽

Vol 16 (34) ◽

pp. 2853-2861

Author(s):

Yanli Li ◽

Rui Yang ◽

Limo Chen ◽

Sufang Wu

Keyword(s):

Multiple Myeloma ◽

Cell Activation ◽

Human Tissues ◽

Transmembrane Glycoprotein ◽

Cell Activation Marker ◽

Research Findings ◽

A Cell ◽

And Function ◽

Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

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The Role of T Cells and Macrophages in Asthma Pathogenesis: A New Perspective on Mutual Crosstalk

Mediators of Inflammation ◽

10.1155/2020/7835284 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Xueyi Zhu ◽

Jie Cui ◽

La Yi ◽

Jingjing Qin ◽

Wuniqiemu Tulake ◽

...

Keyword(s):

T Cells ◽

Cell Activation ◽

Immune Cell ◽

Immune Microenvironment ◽

Innate And Adaptive Immunity ◽

Immune Cell Activation ◽

Inflammatory Signals ◽

Macrophage Dysfunction ◽

New Perspective

Asthma is associated with innate and adaptive immunity mediated by immune cells. T cell or macrophage dysfunction plays a particularly significant role in asthma pathogenesis. Furthermore, crosstalk between them continuously transmits proinflammatory or anti-inflammatory signals, causing the immune cell activation or repression in the immune response. Consequently, the imbalanced immune microenvironment is the major cause of the exacerbation of asthma. Here, we discuss the role of T cells, macrophages, and their interactions in asthma pathogenesis.

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The Role of Leukemia Derived B7-H1 in Tumor-T-Cell Interactions in Humans.

Blood ◽

10.1182/blood.v106.11.4566.4566 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4566-4566

Author(s):

Matthias Krusch ◽

Sabine Wintterle ◽

Lieping Chen ◽

Lothar Kanz ◽

Heinz Wiendl ◽

...

Keyword(s):

T Cell ◽

Cell Lines ◽

T Cell Activation ◽

Cell Activation ◽

Cytokine Production ◽

Leukemia Cells ◽

Human Leukemia ◽

Activation Markers ◽

Murine Leukemia

Abstract Objective: Expression of the B7-homologue B7-H1 (PD1-Ligand) has been proposed to enable tumor cells to evade immune surveillance. Recently, B7-H1 on murine leukemia cells was reported to mediate resistance to cytolytic T-cell destruction. In this study we investigated the expression and functional role of the B7-homologue B7-H1 in human leukemia. Patients and Methods: Leukemia cells from 20 patients and 9 human leukemia cell lines were investigated for B7-H1 expression by flow cytometry. Functional relevance of B7-H1 for tumor-immune interactions was assessed by coculture experiments using purified, alloreactive CD4 and CD8 T-cells in the presence of a neutralizing anti-B7-H1 antibody. Results: Significant B7-H1 expression levels on leukemia cells were detected in 13 of 20 patients and in 8 of 9 cell lines. In contrast to various other tumor entities and the data reported from a murine leukemia system we did not observe any significant inhibitory effect of leukemia-derived B7-H1 on CD4 and CD8 cytokine production (IFN-g, IL-2) or expression of T-cell activation markers (ICOS, CD69). In the presence of a neutralizing B7-H1 antibody (mAb 5H1) no significant changes in T cell IFN-g or IL-2 production were observed. Conclusions: Our data demonstrate that leukemia-derived B7-H1 seems to have no direct influence on T-cell activation and cytokine production in humans. Further experiments are warranted to delineate factors and characterize yet unidentified B7-H1 receptor(s) that determine inhibitory and stimulatory functions of B7-H1 in human leukemia.

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Role of Transmembrane Domain and Cytoplasmic Tail Amino Acid Sequences of Influenza A Virus Neuraminidase in Raft Association and Virus Budding

Journal of Virology ◽

10.1128/jvi.78.10.5258-5269.2004 ◽

2004 ◽

Vol 78 (10) ◽

pp. 5258-5269 ◽

Cited By ~ 80

Author(s):

Subrata Barman ◽

Lopa Adhikary ◽

Alok K. Chakrabarti ◽

Carl Bernas ◽

Yoshihiro Kawaoka ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Influenza A ◽

Transmembrane Domain ◽

Amino Acid Sequences ◽

Type Ii ◽

Virus Growth ◽

Transmembrane Glycoprotein ◽

Virus Life Cycle

ABSTRACT Influenza virus neuraminidase (NA), a type II transmembrane glycoprotein, possesses receptor-destroying activity and thereby facilitates virus release from the cell surface. Among the influenza A viruses, both the cytoplasmic tail (CT) and transmembrane domain (TMD) amino acid sequences of NA are highly conserved, yet their function(s) in virus biology remains unknown. To investigate the role of amino acid sequences of the CT and TMD on the virus life cycle, we systematically mutagenized the entire CT and TMD of NA by converting two to five contiguous amino acids to alanine. In addition, we also made two chimeric NA by replacing the CT proximal one-third amino acids of the NA TMD [NA(1T2N)NA] and the entire NA TMD (NATRNA) with that of human transferrin receptor (TR) (a type II transmembrane glycoprotein). We rescued transfectant mutant viruses by reverse genetics and examined their phenotypes. Our results show that all mutated and chimeric NAs could be rescued into transfectant viruses. Different mutants showed pleiotropic effects on virus growth and replication. Some mutants (NA2A5, NA3A7, and NA4A10) had little effect on virus growth while others (NA3A2, NA5A27, and NA5A31) produced about 50- to 100-fold-less infectious virus and still some others (NA5A14, NA4A19, and NA4A23) exhibited an intermediate phenotype. In general, mutations towards the ectodomain-proximal sequences of TMD progressively caused reduction in NA enzyme activity, affected lipid raft association, and attenuated virus growth. Electron microscopic analysis showed that these mutant viruses remained aggregated and bound to infected cell surfaces and could be released from the infected cells by bacterial NA treatment. Moreover, viruses containing mutations in the extreme N terminus of the CT (NA3A2) as well as chimeric NA containing the TMD replaced partially [NA(1T2N)NA] or fully (NATRNA) with TR TMD caused reduction in virus growth and exhibited the morphological phenotype of elongated particles. These results show that although the sequences of NA CT and TMD per se are not absolutely essential for the virus life cycle, specific amino acid sequences play a critical role in providing structural stability, enzyme activity, and lipid raft association of NA. In addition, aberrant morphogenesis including elongated particle formation of some mutant viruses indicates the involvement of NA in virus morphogenesis and budding.

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ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1

Molecules ◽

10.3390/molecules24224192 ◽

2019 ◽

Vol 24 (22) ◽

pp. 4192 ◽

Cited By ~ 5

Author(s):

Kenneth I. Onyedibe ◽

Modi Wang ◽

Herman O. Sintim

Keyword(s):

Small Molecule ◽

Cyclic Gmp ◽

Small Molecule Inhibitors ◽

Purinergic Signaling ◽

Type Ii ◽

Disease States ◽

Transmembrane Glycoprotein ◽

Nucleotide Pyrophosphatase ◽

Potential Applications

Ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodiesterase that degrades the stimulator of interferon genes (STING) ligand, cyclic GMP–AMP (cGAMP). cGAMP or analogs thereof have emerged as potent immunostimulatory agents, which have potential applications in immunotherapy. This emerging role of ENPP1 has placed this “old” enzyme at the frontier of immunotherapy. This review highlights the roles played by ENPP1, the mechanism of cGAMP hydrolysis by ENPP1, and small molecule inhibitors of ENPP1 with potential applications in diverse disease states, including cancer.

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Fc gamma R(CD16) interaction with ligand induces Ca2+ mobilization and phosphoinositide turnover in human natural killer cells. Role of Ca2+ in Fc gamma R(CD16)-induced transcription and expression of lymphokine genes.

Journal of Experimental Medicine ◽

10.1084/jem.169.2.549 ◽

1989 ◽

Vol 169 (2) ◽

pp. 549-567 ◽

Cited By ~ 136

Author(s):

M A Cassatella ◽

I Anegón ◽

M C Cuturi ◽

P Griskey ◽

G Trinchieri ◽

...

Keyword(s):

Nk Cells ◽

Cell Activation ◽

Cytokine Production ◽

Nk Cell ◽

Stringent Requirement ◽

Mrna Accumulation ◽

Ifn Gamma ◽

Human Natural Killer Cells ◽

Hydrolysis Of

In this study, we present evidence that interaction of Fc gamma R(CD16) with ligands (immune complexes or anti-CD16 antibodies) induces a rapid rise in [Ca2+]i and fast production of both inositol 1,4,5 triphosphate (IP3) and IP4 in homogeneous NK cell preparations. Part of the initial [Ca2+]i rise observed upon stimulation of NK cells with either anti-CD16 antibodies alone or after their crosslinking at the cell membrane depends on Ca2+ mobilization from intracellular stores, but sustained [Ca2+]i levels are maintained, after the initial spike, through influx of extracellular Ca2+. The [Ca2+]i rise is mediated, at least in part, by increases in IP3 after receptor-induced hydrolysis of membrane polyphosphoinositides (PPI). The role of extracellular Ca2+ in Fc gamma R(CD16)-dependent induction of lymphokine gene expression has been tested by evaluating production, mRNA accumulation and transcription of IFN-gamma and TNF in NK cells stimulated with Fc gamma R(CD16) ligands and/or rIL-2 in the presence of EGTA. Under these conditions, accumulation and transcription of both IFN-gamma and TNF mRNA induced by CD16 ligands, but not that induced by rIL-2, is completely abolished and neither cytokine can be detected at significant levels in the supernatant fluids of cells so treated. These data confirm that NK cell activation by specific ligands occurs through mechanisms distinct from those induced by IL-2, and indicate that extracellular Ca2+ represents a stringent requirement for cytokine production induced in NK cells through specific (Fc gamma R) stimulation. Our data also indicate that the [Ca2+]i rise induced upon Fc gamma R(CD16) crosslinking, though necessary, is not sufficient per se to induce activation of lymphokine genes, compatible with the hypothesis that Fc gamma R(CD16) crosslinking generates additional transducing signals that synergize with IL-2 to maximally activate NK cells.

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Protein Kinase C θ Is Not Essential for T-Cell-Mediated Clearance of Murine Gammaherpesvirus 68

Journal of Virology ◽

10.1128/jvi.79.11.6808-6813.2005 ◽

2005 ◽

Vol 79 (11) ◽

pp. 6808-6813 ◽

Cited By ~ 31

Author(s):

Francesca Giannoni ◽

Ashley B. Lyon ◽

Mark D. Wareing ◽

Peter B. Dias ◽

Sally R. Sarawar

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cytokine Production ◽

Viral Clearance ◽

Murine Gammaherpesvirus ◽

Kinase C ◽

Gammaherpesvirus 68 ◽

Murine Gammaherpesvirus 68

ABSTRACT Murine gammaherpesvirus 68 (MHV-68) is a naturally occurring rodent pathogen with significant homology to human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. T cells are essential for primary clearance of MHV-68 and survival of mice following intranasal infection. Previous reports have suggested that protein kinase C θ (PKCθ) is essential for T-cell activation and cytokine production in vitro. To determine the role of this molecule in vivo during the immune response to a viral infection, PKCθ−/− mice were infected with MHV-68. Despite the essential role of T cells in viral clearance, PKCθ−/− mice survived infection, cleared lytic virus, and maintained effective long-term control of latency. CD8 T-cell expansion, trafficking to the lung, and cytotoxic activity were similar in PKCθ+/+ and PKCθ−/− mice, whereas antiviral antibody and T-helper cell cytokine production were significantly lower in PKCθ−/− mice than in PKCθ+/+ mice. These studies demonstrate a differential requirement for PKCθ in the immune response to MHV-68 and show that PKCθ is not essential for the T-cell activation events leading to viral clearance.

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Monocytes as Regulators of Inflammation and HIV-Related Comorbidities during cART

Journal of Immunology Research ◽

10.1155/2014/569819 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 47

Author(s):

Joshua J. Anzinger ◽

Tiffany R. Butterfield ◽

Thomas A. Angelovich ◽

Suzanne M. Crowe ◽

Clovis S. Palmer

Keyword(s):

Hiv Infection ◽

T Cell Activation ◽

Immune Activation ◽

Cell Activation ◽

The Elderly ◽

Chronic Immune Activation ◽

Monocyte Activation ◽

Combined Antiretroviral Therapy

Combined antiretroviral therapy (cART) extends the lifespan and the quality of life for HIV-infected persons but does not completely eliminate chronic immune activation and inflammation. The low level of chronic immune activation persisting during cART-treated HIV infection is associated with the development of diseases which usually occur in the elderly. Although T-cell activation has been extensively examined in the context of cART-treated HIV infection, monocyte activation is only beginning to be recognized as an important source of inflammation in this context. Here we examine markers and sources of monocyte activation during cART-treated HIV infection and discuss the role of monocytes during cardiovascular disease, HIV-associated neurocognitive disorder, and innate immune aging.

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