Membrane cofactor protein (MCP; CD46): deficiency states and pathogen connections

Liszewski, M. Kathryn; Atkinson, John P.

doi:10.1016/j.coi.2021.04.005

Cited by 50 publications

(31 citation statements)

References 77 publications

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“…A recent study has revealed that pharmacological modulation of autophagy might affect the therapeutic efficacy of PD-L1 blockade in GC ( Wang et al, 2019 ). Interestingly, a growing body of studies identified that CD46, a variable involved in our risk model with a negative coefficient, exerted an essential role in modulating the effector function of T cells ( Arbore et al, 2018 ; Liszewski and Atkinson 2021 ). In consistency with previous investigation that immunomodulatory interactions between the autophagy and cancer ( Jacquin and Apetoh 2018 ; Xia et al, 2021 ), we also identified that dysfunctional characteristics enriched in the autophagy-associated high-risk group and the low-risk group exhibited high expression of immune checkpoint gene markers and genes associated with the CD8 + T-cell–mediated cytotoxicity than those in the high risk group.…”

Section: Disscussionmentioning

confidence: 99%

Prognostic Autophagy-Related Model Revealed by Integrating Single-Cell RNA Sequencing Data and Bulk Gene Profiles in Gastric Cancer

Tong

Zhang

Zhu

et al. 2022

Front. Cell Dev. Biol.

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Autophagy has been associated with tumor progression, prognosis, and treatment response. However, an autophagy-related model and their clinical significance have not yet been fully elucidated. In the present study, through the integrative analysis of bulk RNA sequencing and single-cell RNA sequencing, an autophagy-related risk model was identified. The model was capable of distinguishing the worse prognosis of patients with gastric cancer (GC), which was validated in TCGA and two independent Gene Expression Omnibus cohorts utilizing the survival analysis, and was also independent of other clinical covariates evaluated by multivariable Cox regression. The clinical value of this model was further assessed using a receiver operating characteristic (ROC) and nomogram analysis. Investigation of single-cell RNA sequencing uncovered that this model might act as an indicator of the dysfunctional characteristics of T cells in the high-risk group. Moreover, the high-risk group exhibited the lower expression of immune checkpoint markers (PDCD1 and CTLA4) than the low-risk group, which indicated the potential predictive power to the current immunotherapy response in patients with GC. In conclusion, this autophagy-associated risk model may be a useful tool for prognostic evaluation and will facilitate the potential application of this model as an indicator of the predictive immune checkpoint biomarkers.

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Section: Disscussionmentioning

confidence: 99%

Prognostic Autophagy-Related Model Revealed by Integrating Single-Cell RNA Sequencing Data and Bulk Gene Profiles in Gastric Cancer

Tong

Zhang

Zhu

et al. 2022

Front. Cell Dev. Biol.

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“…Deleting the entire CD46 gene in vivo would likely have severe deleterious consequences. In most mammals, CD46 is ubiquitously expressed on all nucleated cells and is critical in several diverse biological processes 16 . The essential roles for CD46 function include complement inactivation, modulation of T-cell activation, and fertility 17,18 .…”

Section: Introductionmentioning

confidence: 99%

First gene-edited calf with reduced susceptibility to a major viral pathogen

Workman

Heaton

Ley

et al. 2022

Preprint

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Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 16 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in CD46 may reduce the burden of BVDV-associated diseases in cattle, and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones.

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“…Согласно литературе, вирус SARS-Cov-2 может проникать в клетки не только с помощью S1 вирусного шипового (S) белка через связывание с ACE2, но и через другие рецепторы клеток. К таким кандидатным рецепторам относится CD46, который, так же как и CD45, относится к панлейкоцитарным рецепторам и экспрессируется на всех видах лимфоцитов [8,11]. CD46 представляет собой мембранный гликопротеин I типа, экспрессируемый на всех ядерных клетках, характеризующийся как регуляторный белок комплемента и как рецептор для ряда патогенов человека, включая вакцинный штамм вируса кори, аденовирусов (группы B и D) и вирусов герпеса 6 типа [12].…”

Section: Introductionunclassified

Studies of CD45+ and CD46+ expression on the peripheral blood lymphocyte subsets of the post-COVID patients

Добрынина

Зурочка

Komelkova

et al. 2022

Russian Journal of Immunology

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The SARS-CoV-2 virus can enter the cells using S1 viral spike (S) protein, not only by binding to ACE2, but also through other cellular receptors. These candidate receptors include CD46, which, like CD45, belongs to pan-leukocyte receptors and is expressed on all types of lymphocytes. In turn, SARS-CoV-2 infection is accompanied by damage to almost all compartments of the immune system, mainly T lymphocytes. The purpose of the study was to evaluate the expression levels of CD45+ and CD46+ in various subpopulations of lymphocytes in patients who had undergone SARS-CoV-2 infection. 72 patients who had undergone SARS-CoV-2 infection were examined. Using flow cytometry technique, we determined CD45+ and CD46+ (panleukocyte marker for lymphocyte gating), CD45+ and CD46+, CD3+ (T lymphocytes), CD45+ and CD46+, CD3+, CD4+ (helper inducers), CD45+ and CD46+, CD3+, CD8+ (cytotoxic T-lymphocytes), CD45+ and CD46+, CD3+, CD56+ (TNK cells) CD45+ and CD46+, CD3-, CD56+ (natural killers), CD45+ and CD46+, CD3-, CD19+ (B lymphocytes), CD45+ and CD46+, CD3+, CD4+, CD25+ (activated helpers, early activation of lymphocytes), CD45+ and CD46+, CD3+, HLA-DR (activated T lymphocytes late activation of lymphocytes). Our studies have shown that a decrease in CD46+ expression in T lymphocytes (CD3+) is accompanied by similar decrease of its expression in cytotoxic T lymphocytes (CD3+, CD8+), TNK (CD3+, CD56+), as well as in helpers T carrying markers of early activation (CD3+, CD4+, CD25+). At the same time, the most pronounced decrease was observed both among total T lymphocytes and cytotoxic T cells. In these patients, the expression level of CD46+ in B lymphocytes was slightly increased. Recent data suggest that there is no involvement of CD46 receptor on B lymphocytes. Our data suggest that the SARS-CoV-2 virus may affect the CD46 receptor. Such exposure may lead to promotion of the long-COVID (post-COVID) symptoms in such patients, thus requiring new approaches to correction of these disorders.

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Membrane cofactor protein (MCP; CD46): deficiency states and pathogen connections

Abstract: Graphical abstract

Cited by 50 publications

References 77 publications

Prognostic Autophagy-Related Model Revealed by Integrating Single-Cell RNA Sequencing Data and Bulk Gene Profiles in Gastric Cancer

Prognostic Autophagy-Related Model Revealed by Integrating Single-Cell RNA Sequencing Data and Bulk Gene Profiles in Gastric Cancer

First gene-edited calf with reduced susceptibility to a major viral pathogen

Studies of CD45+ and CD46+ expression on the peripheral blood lymphocyte subsets of the post-COVID patients

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