Mechanisms of Human Immunodeficiency Virus-Associated Lymphocyte Regulated Cell Death

Paim, Ana C.; Badley, Andrew D.; Cummins, Nathan W.

doi:10.1089/aid.2019.0213

Cited by 13 publications

(11 citation statements)

References 132 publications

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“…The death of these lymphocytes is the root cause of acquired immunodeficiency syndrome (AIDS). What was thought to be the main mechanism of CD4+ T cell depletion is programmed cell death (apoptosis) [ 1 ]. Laboratory-adapted HIV strains lead to productive infection and ultimately apoptotic death in CD4+ T cells.…”

Section: Introductionmentioning

confidence: 99%

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy

Shi

Zhang

2022

Computational and Mathematical Methods in Medicine

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Human immunodeficiency virus (HIV) infection is characterized not only by severe immunodeficiency but also by persistent inflammation and immune activation. These characteristics persist in people living with HIV (PLHIV) receiving effective antiretroviral therapy (ART) and are associated with morbidity and mortality in nonacquired immunodeficiency syndrome (AIDS) events. ART can inhibit HIV replication and promote immune reconstitution, which is currently the most effective way to control AIDS. However, despite effective long-term ART and overall suppression of plasma HIV RNA level, PLHIV still shows chronic low-level inflammation. The exact mechanisms that trigger chronic inflammation are unknown. Activation of the inflammasome is essential for the host response to pathogens, and some recent studies have confirmed the role of the inflammasome in the pathogenesis of inflammatory diseases. The NLRP3 inflammasome has been widely studied, which is a pyrin domain-containing protein 3 belonging to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent studies suggest that inflammasome-mediated pyroptosis is associated with CD4+ T cell loss in the absence of persistent infectious HIV replication. This article reviews the mechanism of the NLRP3 inflammasome and its correlation with immune reconstitution in PLHIV treated with ART.

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Section: Introductionmentioning

confidence: 99%

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy

Shi

Zhang

2022

Computational and Mathematical Methods in Medicine

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“…Mitochondria are the regulatory center of apoptosis and the site of the well-known intrinsic apoptosis pathway [ 35 ]. Apoptosis is regulated by external forces, such as death receptor signaling, and also intracellular milieu [ 36 ]. Apoptosis-inducing factor is a novel mediator in apoptosis and the most frequently studied tracer is Annexin-V [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of RELL2 as a Potential Biomarker Associated with Tumor Immune Infiltrating Cells in a Pan-Cancer Analysis

Musha

Ablikim³

et al. 2022

Disease Markers

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Background. Receptor expressed in lymphoid tissues-like 2 (RELL2), which is a member of RELT family, is closely associated with the plasma membrane and acts as a modulator for RELT signaling. Overexpression of RELL2 induces the activation of MAPK14/p38 cascade and apoptosis. However, whether RELL2 contributes to cancers remains unclear. Here, we examined its role in cancer patient prognosis and various tumors. Methods. We used several bioinformatics methods, specifically gene set enrichment analysis (GSEA), ScanNeo, and ESTIMATE, to analyze the CCLE dataset, GTEx dataset, and TCGA dataset. We investigated the possible association of RELL2 with the microsatellite instability (MSI) of various tumors, tumor mutational burden (TMB), immune checkpoint, immune neoantigens, immune microenvironment, and patient prognosis. Result. RELL2 is highly expressed in cancer compared with normal tissues. RELL2 expression is linked with worse progression-free interval and overall survival in numerous cancers. In most cancers, high RELL2 expression was related to a poor prognosis. RELL2 expression was significantly associated with the tumor microenvironment, MSI, and TMB. RELL2 expression is strongly associated with phenotypes that are of major clinical significance, particularly those associated with immune neoantigens and the expression profiles of immune checkpoint genes in pan-cancer. RELL2 expression strongly linked with the expressions of methyltransferases and DNA repair genes. It also significantly correlated with multiple signaling pathways through gene set enrichment analysis. Conclusion. RELL2 may be a prognostic biomarker in pan-cancer and may have an important function in tumorigenesis and progression.

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“…However, evaluation of LRA function on macrophage populations is critical since the transcription factors that regulate HIV latency and maintenance in macrophages are distinct from those in CD4+ T cells [209,210]. In addition, inherent enhanced resistance to apoptosis and HIV-cytopathic effects [211], constitute critical differences compared to CD4+ T cell reservoirs that constitute additional challenges to achieve a complete cure.…”

Section: Reactivating Latency From Macrophage Reservoirsmentioning

confidence: 99%

HIV Latency in Myeloid Cells: Challenges for a Cure

et al. 2022

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The use of antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) treatment has been highly successful in controlling plasma viremia to undetectable levels. However, a complete cure for HIV is hindered by the presence of replication-competent HIV, integrated in the host genome, that can persist long term in a resting state called viral latency. Resting memory CD4+ T cells are considered the biggest reservoir of persistent HIV infection and are often studied exclusively as the main target for an HIV cure. However, other cell types, such as circulating monocytes and tissue-resident macrophages, can harbor integrated, replication-competent HIV. To develop a cure for HIV, focus is needed not only on the T cell compartment, but also on these myeloid reservoirs of persistent HIV infection. In this review, we summarize their importance when designing HIV cure strategies and challenges associated to their identification and specific targeting by the “shock and kill” approach.

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Mechanisms of Human Immunodeficiency Virus-Associated Lymphocyte Regulated Cell Death

Cited by 13 publications

References 132 publications

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy

Comprehensive Analysis of RELL2 as a Potential Biomarker Associated with Tumor Immune Infiltrating Cells in a Pan-Cancer Analysis

HIV Latency in Myeloid Cells: Challenges for a Cure

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