Lymphocyte‐specific protein 1 (LSP1) regulates bone marrow stromal cell antigen 2 (BST‐2)‐mediated intracellular trafficking of HIV‐1 in dendritic cells

Kulkarni, Rutuja; Jiang, Shuxian; Birrane, Gabriel

doi:10.1002/1873-3468.13788

Cited by 3 publications

(4 citation statements)

References 49 publications

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“…Interestingly, a study reported found that cases with RA achieved declining LSP1 expressing state within peripheral T cell with improved migratory ability, thereby demonstrating that defects within LSP1 signaling lead to the decline of T-cell activation threshold (46). Kulkarni et al reported that LSP1 underwent the interacting process with the interferon-inducible protein inside dendritic cell for facilitating surface-bound HIV-1 endocytosis and early endosome forming processes (47). Granulysin refers to one protein in the granules of natural killer cell and human cytotoxic T lymphocyte, exhibiting cytolysis activity against tumor and microbe (32), whereas there is no information concerning the mechanisms involved in RA.…”

Section: Discussionmentioning

confidence: 99%

Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies

Yu¹,

Zhang²,

Zhuo³

et al. 2021

Front. Immunol.

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BackgroundRheumatoid arthritis (RA) refers to an autoimmune rheumatic disease that imposes a huge burden on patients and society. Early RA diagnosis is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. In the present study, the aim was at examining RA’s diagnostic signatures and the effect of immune cell infiltration in this pathology.MethodsGene Expression Omnibus (GEO) database provided three datasets of gene expressions. Firstly, this study adopted R software for identifying differentially expressed genes (DEGs) and conducting functional correlation analyses. Subsequently, we integrated bioinformatic analysis and machine-learning strategies for screening and determining RA’s diagnostic signatures and further verify by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. Moreover, this study employed cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) website for assessing the inflammatory state of RA, and an investigation was conducted on the relationship of diagnostic signatures and infiltrating immune cells.ResultsOn the whole, 54 robust DEGs received the recognition. Lymphocyte-specific protein 1 (LSP1), Granulysin (GNLY), and Mesenchymal homobox 2 (MEOX2) (AUC = 0.955) were regarded as RA’s diagnostic markers and showed their statistically significant difference by qRT-PCR. As indicated from the immune cell infiltration analysis, resting NK cells, neutrophils, activated NK cells, T cells CD8, memory B cells, and M0 macrophages may be involved in the development of RA. Additionally, all diagnostic signatures might be different degrees of correlation with immune cells.ConclusionsIn conclusion, LSP1, GNLY, and MEOX2 are likely to be available in terms of diagnosing and treating RA, and the infiltration of immune cells mentioned above may critically impact RA development and occurrence.

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Section: Discussionmentioning

confidence: 99%

Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies

Yu¹,

Zhang²,

Zhuo³

et al. 2021

Front. Immunol.

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“…These virions either are endocytosed and transported for degradation or enhance cell-to-cell spread of infection. The trapped virions-BST2 complex is proposed to be endocytosed via interaction with actin-binding protein lymphocyte-specific protein 1 (LSP1) ( Kulkarni et al., 2020 ). Based on structural analysis and reasonable assumption, the LSP1/BST2 interaction would be dependent on the LSP1 N-terminal domain and YxY motif of BST2, known to interact with the actin cytoskeleton ( Mahauad-Fernandez and Okeoma, 2016 ; Kulkarni et al., 2020 ).…”

Section: Classical Function Of Bst2: Trapping Hiv-1mentioning

confidence: 99%

“…The trapped virions-BST2 complex is proposed to be endocytosed via interaction with actin-binding protein lymphocyte-specific protein 1 (LSP1) ( Kulkarni et al., 2020 ). Based on structural analysis and reasonable assumption, the LSP1/BST2 interaction would be dependent on the LSP1 N-terminal domain and YxY motif of BST2, known to interact with the actin cytoskeleton ( Mahauad-Fernandez and Okeoma, 2016 ; Kulkarni et al., 2020 ). After internalization, most of the HIV-1 is degraded in lysosomes, with the remaining minority retained in endocytic compartments and depleted through the proteasome pathway ( Smith et al., 2007 ).…”

Section: Classical Function Of Bst2: Trapping Hiv-1mentioning

confidence: 99%

Multi-functional BST2/tetherin against HIV-1, other viruses and LINE-1

Zhao

Wang

et al. 2022

Front. Cell. Infect. Microbiol.

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Bone marrow stromal cell antigen 2 (BST2), also known as CD317, HM1.24, or tetherin, is a type II transmembrane glycoprotein. Its expression is induced by IFN-I, and it initiates host immune responses by directly trapping enveloped HIV-1 particles onto the cell surface. This antagonistic mechanism toward the virus is attributable to the unique structure of BST2. In addition to its antiviral activity, BST2 restricts retrotransposon LINE-1 through a distinct mechanism. As counteractive measures, different viruses use a variety of proteins to neutralize the function or even stability of BST2. Interestingly, BST2 seems to have both a positive and a negative influence on immunomodulation and virus propagation. Here, we review the relationship between the structural and functional bases of BST2 in anti-HIV-1 and suppressing retrotransposon LINE-1 activation and focus on its dual features in immunomodulation and regulating virus propagation.

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“…BST-2, in addition to its functions at the cell membrane, is also known to anchor HIV-1 into the endosomal membrane and regulate intracellular trafficking of virus containing vesicles towards phagolysosomal complexes [45]. We thus investigated the interaction of BST-2 with components of intracellular trafficking and ESCRT machinery in HIV-1 infected cells.…”

Section: Cocaine Alters Bst-2 Interaction With Endosome Biogenesis Es...mentioning

confidence: 99%

Cocaine augments neuro-inflammation via modulating extracellular vesicle release in HIV-1 infected immune cells

et al. 2021

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Background Extracellular Vesicles (EV) recently have been implicated in the pathogenesis of HIV-1 syndromes, including neuroinflammation and HIV-1 associated neurological disorder (HAND). Cocaine, an illicit stimulant drug used worldwide is known to exacerbate these HIV-1 associated neurological syndromes. However, the effects of cocaine on EV biogenesis and roles of EVs in enhancing HIV-1 pathogenesis are not yet well defined. Results Here, we investigated the effects of cocaine on EV biogenesis and release in HIV-1 infected immune cells and explored their roles in elicitation of neuroinflammation. We found that cocaine significantly augmented the release of EVs from uninfected and HIV-1 infected T-cells, DCs and macrophages. Further analysis of the molecular components of EVs revealed enhanced expression of adhesion molecules integrin β1 and LFA-1 in those EVs derived from cocaine treated cells. Intriguingly, in EVs derived from HIV-1 infected cells, cocaine treatment significantly increased the levels of viral genes in EVs released from macrophages and DCs, but not in T-cells. Exploring the molecular mechanism to account for this, we found that DCs and macrophages showed enhanced expression of the cocaine receptor Sigma 1-Receptor compared to T-cells. In addition, we found that cocaine significantly altered the integrity of the RNA-induced silencing complex (RISC) in HIV-1 infected macrophages and DCs compared to untreated HIV-1 infected cells. Characterizing further the molecular mechanisms involved in how cocaine increased EV release, we found that cocaine decreased the expression of the interferon-inducible protein BST-2; this resulted in altered trafficking of intracellular virus containing vesicles and EV biogenesis and release. We also observed EVs released from cocaine treated HIV-1 infected macrophages and DCs enhanced HIV-1 trans-infection to T-cells compared to those from untreated and HIV-1 infected cells. These EVs triggered release of proinflammatory cytokines in human brain microvascular endothelial cells (HBMECs) and altered monolayer integrity. Conclusions Taken together, our results provide a novel mechanism which helps to elucidate the enhanced prevalence of neurological disorders in cocaine using HIV-1 infected individuals and offers insights into developing novel therapeutic strategies against HAND in these hosts.

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Lymphocyte‐specific protein 1 (LSP1) regulates bone marrow stromal cell antigen 2 (BST‐2)‐mediated intracellular trafficking of HIV‐1 in dendritic cells

Cited by 3 publications

References 49 publications

Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies

Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies

Multi-functional BST2/tetherin against HIV-1, other viruses and LINE-1

Cocaine augments neuro-inflammation via modulating extracellular vesicle release in HIV-1 infected immune cells

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