Bibliographies thématiques / HIV-1, HLA-C

Littérature scientifique sur le sujet « HIV-1, HLA-C »

Auteur : Grafiati
Publié le 11 mars 2023

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Articles de revues sur le sujet "HIV-1, HLA-C"

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Zipeto, Donato, et Alberto Beretta. « C3 HIV-1 Env and HLA-C ». JAIDS Journal of Acquired Immune Deficiency Syndromes 59 (avril 2012) : 77. http://dx.doi.org/10.1097/01.qai.0000413798.79651.e7.

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Apps, Richard, Gregory Q. Del Prete, Pramita Chatterjee, Abigail Lara, Zabrina L. Brumme, Mark A. Brockman, Stuart Neil et al. « HIV-1 Vpu Mediates HLA-C Downregulation ». Cell Host & ; Microbe 19, no 5 (mai 2016) : 686–95. http://dx.doi.org/10.1016/j.chom.2016.04.005.

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Barker, Edward, et David T. Evans. « HLA-C Downmodulation by HIV-1 Vpu ». Cell Host & ; Microbe 19, no 5 (mai 2016) : 570–71. http://dx.doi.org/10.1016/j.chom.2016.04.023.

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Muccini, Camilla, Monica Guffanti, Vincenzo Spagnuolo, Massimo Cernuschi, Laura Galli, Alba Bigoloni, Andrea Galli, Andrea Poli, Sara Racca et Antonella Castagna. « Association between low levels of HIV-1 DNA and HLA class I molecules in chronic HIV-1 infection ». PLOS ONE 17, no 3 (15 mars 2022) : e0265348. http://dx.doi.org/10.1371/journal.pone.0265348.

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Background HLA-B27 and -B57 were found in people with low levels of HIV-1 DNA, suggesting that HLA class I molecules may influence the size of HIV-1 reservoir. Aim of the study was to explore the association between HLA class I molecules and HIV-1 DNA in people with chronic HIV-1 infection. Methods Post-hoc analysis of the APACHE trial, on adults with chronic HIV-1 infection, prolonged suppressive antiretroviral therapy and good immunological profile. HIV-1 DNA was quantified in peripheral blood mononuclear cells (PBMCs); HLA-A, -B and -C were tested on genomic DNA. Crude odds ratios (OR) with their respective 95% Wald confidence intervals (95% CIs) were estimated by univariable logistic regression for HLAs with a p-value <0.10. Results We found 78 and 18 patients with HIV-1 DNA ≥100 copies/106PBMCs and with HIV-1 DNA <100 copies/106PBMCs, respectively. HLA-A24 was present in 21 (29.6%) participants among subjects with HIV-1 DNA ≥100 copies/106PBMCs and 1 (5.9%) among those with HIV-1 DNA <100 copies/106PBMCs (OR = 5.67, 95%CI = 0.79–46.03; p = 0.105); HLA-B39 was present in 1 (1.4%) with HIV-1 DNA ≥100 copies/106PBMCs and in 3 (17.6%) with HIV-1 DNA <100 copies/106PBMCs (OR = 13.71, 95%CI = 1.33–141.77; p = 0.028) and HLA-B55 in 3 (4.2%) and 3 (17.6%), respectively (OR = 4.43, 95%CI = 0.81–24.29; p = 0.087). All the three patients with HLA-B39 and HIV-1 DNA <100 copies/106PBMCs did not have HLA-A24. Conclusions In patients with HIV-1 infection who maintained a good virological and immunological profile, HLA-B39 and -B55 may be associated with lower levels of HIV-1 DNA.
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Bachtel, Nathaniel D., Gisele Umviligihozo, Suzanne Pickering, Talia M. Mota, Hua Liang, Gregory Q. Del Prete, Pramita Chatterjee et al. « HLA-C downregulation by HIV-1 adapts to host HLA genotype ». PLOS Pathogens 14, no 9 (4 septembre 2018) : e1007257. http://dx.doi.org/10.1371/journal.ppat.1007257.

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Specht, Anke, Amalio Telenti, Raquel Martinez, Jacques Fellay, Elizabeth Bailes, David T. Evans, Mary Carrington, Beatrice H. Hahn, David B. Goldstein et Frank Kirchhoff. « Counteraction of HLA-C-Mediated Immune Control of HIV-1 by Nef ». Journal of Virology 84, no 14 (12 mai 2010) : 7300–7311. http://dx.doi.org/10.1128/jvi.00619-10.

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ABSTRACT A host genetic variant (−35C/T) correlates with increased human leukocyte antigen C (HLA-C) expression and improved control of HIV-1. HLA-C-mediated immunity may be particularly protective because HIV-1 is unable to remove HLA-C from the cell surface, whereas it can avoid HLA-A- and HLA-B-mediated immunity by Nef-mediated down-modulation. However, some individuals with the protective −35CC genotype exhibit high viral loads. Here, we investigated whether the ability of HIV-1 to replicate efficiently in the “protective” high-HLA-C-expression host environment correlates with specific functional properties of Nef. We found that high set point viral loads (sVLs) were not associated with the emergence of Nef variants that had acquired the ability to down-modulate HLA-C or were more effective in removing HLA-A and HLA-B from the cell surface. However, in individuals with the protective −35CC genotype we found a significant association between sVLs and the efficiency of Nef-mediated enhancement of virion infectivity and modulation of CD4, CD28, and the major histocompatibility complex class II (MHC-II)-associated invariant chain (Ii), while this was not observed in subjects with the −35TT genotype. Since the latter Nef functions all influence the stimulation of CD4+ T helper cells by antigen-presenting cells, they may cooperate to affect both the activation status of infected T cells and the generation of an antiviral cytotoxic T-lymphocyte (CTL) response. In comparison, different levels of viremia in individuals with the common −35TT genotype were not associated with differences in Nef function but with differences in HLA-C mRNA expression levels. Thus, while high HLA-C expression may generally facilitate control of HIV-1, Nef may counteract HLA-C-mediated immune control in some individuals indirectly, by manipulating T-cell function and MHC-II antigen presentation.
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Adnan, Sama, Arumugam Balamurugan, Alicja Trocha, Michael S. Bennett, Hwee L. Ng, Ayub Ali, Christian Brander et Otto O. Yang. « Nef interference with HIV-1–specific CTL antiviral activity is epitope specific ». Blood 108, no 10 (15 novembre 2006) : 3414–19. http://dx.doi.org/10.1182/blood-2006-06-030668.

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AbstractHIV-1 Nef and HIV-1–specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HLA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HLA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C–restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A– and HLA-B– versus HLA-C–restricted CTLs in vivo. The data thus indicate that HLA-C–restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C–restricted CTLs for immunotherapy or vaccine development.
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Nii-Trebi, Nicholas I., Saori Matsuoka, Ai Kawana-Tachikawa, Evelyn Y. Bonney, Christopher Z. Abana, Sampson B. Ofori, Taketoshi Mizutani et al. « Super high-resolution single-molecule sequence-based typing of HLA class I alleles in HIV-1 infected individuals in Ghana ». PLOS ONE 17, no 6 (2 juin 2022) : e0269390. http://dx.doi.org/10.1371/journal.pone.0269390.

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Polymorphisms in human leukocyte antigen (HLA) class I loci are known to have a great impact on disease progression in HIV-1 infection. Prevailing HIV-1 subtypes and HLA genotype distribution are different all over the world, and the HIV-1 and host HLA interaction could be specific to individual areas. Data on the HIV-1 and HLA interaction have been accumulated in HIV-1 subtype B- and C-predominant populations but not fully obtained in West Africa where HIV-1 subtype CRF02_AG is predominant. In the present study, to obtain accurate HLA typing data for analysis of HLA association with disease progression in HIV-1 infection in West African populations, HLA class I (HLA-A, -B, and -C) four-digit allele typing was performed in treatment-naïve HIV-1 infected individuals in Ghana (n = 324) by a super high-resolution single-molecule sequence-based typing (SS-SBT) using next-generation sequencing. Comparison of the SS-SBT-based data with those obtained by a conventional sequencing-based typing (SBT) revealed incorrect assignment of several alleles by SBT. Indeed, HLA-A*23:17, HLA-B*07:06, HLA-C*07:18, and HLA-C*18:02 whose allele frequencies were 2.5%, 0.9%, 4.3%, and 3.7%, respectively, were not determined by SBT. Several HLA alleles were associated with clinical markers, viral load and CD4+ T-cell count. Of note, the impact of HLA-B*57:03 and HLA-B*58:01, known as protective alleles against HIV-1 subtype B and C infection, on clinical markers was not observed in our cohort. This study for the first time presents SS-SBT-based four-digit typing data on HLA-A, -B, and -C alleles in Ghana, describing impact of HLA on viral load and CD4 count in HIV-1 infection. Accumulation of these data would facilitate high-resolution HLA genotyping, contributing to our understanding of the HIV-1 and host HLA interaction in Ghana, West Africa.
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Ende, Zachary, Martin J. Deymier, Daniel T. Claiborne, Jessica L. Prince, Daniela C. Mónaco, William Kilembe, Susan A. Allen et Eric Hunter. « HLA Class I Downregulation by HIV-1 Variants from Subtype C Transmission Pairs ». Journal of Virology 92, no 7 (10 janvier 2018) : e01633-17. http://dx.doi.org/10.1128/jvi.01633-17.

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ABSTRACTHIV-1 downregulates human leukocyte antigen A (HLA-A) and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing natural killer (NK) cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B, and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA-C, and total HLA class I downregulation by flow cytometry of primary CD4 T cells infected with 40 infectious molecular clones. Primary viruses mediated a range of HLA class I downregulation capacities (1.3- to 6.1-fold) which could differ significantly between transmission pairs. Downregulation of HLA-C surface expression on infected cells correlated with susceptibility toin vitroNK cell suppression of virus release. Despite this, transmitted/founder variants did not share a downregulation signature and instead were more similar to the quasispecies of matched donor partners. These data indicate that a range of viral abilities to downregulate HLA-A, HLA-B, and HLA-C exist within and between individuals that can have functional consequences on immune recognition.IMPORTANCESubtype C HIV-1 is the predominant subtype involved in heterosexual transmission in sub-Saharan Africa. Authentic subtype C viruses that contain natural sequence variations throughout the genome often are not used in experimental systems due to technical constraints and sample availability. In this study, authentic full-length subtype C viruses, including transmitted/founder viruses, were examined for the ability to disrupt surface expression of HLA class I molecules, which are central to both adaptive and innate immune responses to viral infections. We found that the HLA class I downregulation capacity of primary viruses varied, and HLA-C downregulation capacity impacted viral suppression by natural killer cells. Transmitted viruses were not distinct in the capacity for HLA class I downregulation or natural killer cell evasion. These results enrich our understanding of the phenotypic variation existing among natural HIV-1 viruses and how that might impact the ability of the immune system to recognize infected cells in acute and chronic infection.
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Stefani, Chiara, Antonella Sangalli, Elena Locatelli, Tania Federico, Giovanni Malerba, Maria Grazia Romanelli, Gustavo Adolfo Argañaraz et al. « Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients ». International Journal of Molecular Sciences 23, no 23 (27 novembre 2022) : 14852. http://dx.doi.org/10.3390/ijms232314852.

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HIV-1 infection in the absence of treatment results in progression toward AIDS. Host genetic factors play a role in HIV-1 pathogenesis, but complete knowledge is not yet available. Since less-expressed HLA-C variants are associated with poor HIV-1 control and unstable HLA-C variants are associated with higher HIV-1 infectivity, we investigated whether there was a correlation between the different stages of HIV-1 progression and the presence of specific HLA-C allotypes. HLA-C genotyping was performed using allele-specific PCR by analyzing a treatment-naïve cohort of 96 HIV-1-infected patients from multicentric cohorts in the USA, Canada, and Brazil. HIV-1-positive subjects were classified according to their different disease progression status as progressors (Ps, n = 48), long-term non-progressors (LTNPs, n = 37), and elite controllers (ECs, n = 11). HLA-C variants were classified as stable or unstable according to their binding stability to β2-microglobulin/peptide complex. Our results showed a significant correlation between rapid progression to AIDS and the presence of two or one unstable HLA-C variants (p-value: 0.0078, p-value: 0.0143, respectively). These findings strongly suggest a link between unstable HLA-C variants both at genotype and at allele levels and rapid progression to AIDS. This work provides further insights into the impact of host genetic factors on AIDS progression.
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Thèses sur le sujet "HIV-1, HLA-C"

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Honeyborne, Isobella W. A. « Definition of HLA-B and HLA-C-restricted CD8+ T cell responses and their contribution to immune control of HIV-1 infection ». Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504481.

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Corrah, Tumena Wandifa. « A study of the phenotype and function of HLA-C restricted CD8 T cells in HIV-1 infection ». Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:456f2b57-55de-42ed-83ac-bcbd1d869bd0.

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A recent study showed that a polymorphism ~35kb upstream of the HLA-C gene (-35 SNP) correlates with host control of HIV-1 in Caucasians, with the minor allele (C) associating with significantly lower set point viral loads than the major allele (T). A link between viral load and HLA-C is suggested by linkage of the two SNP alleles with different HLA-C alleles and by the fact that HLA-C, in contrast to HLA-A and -B, is not down-regulated by HIV-1 Nef protein. In addition, the -35C variant has been shown to associate with higher HLA-C messenger RNA expression in EBV-transformed B cell lines. We initially propose that increased surface expression of HLA-C in subjects with the protective SNP leads to increased breadth and magnitude of HLA-C restricted T cell responses, explaining the decrease in viral load in these subjects. This study initially investigates whether the -35 SNP correlates with the surface level of HLA-C using the monoclonal antibodies DT9, which recognises both HLA-C and HLA-E, and 3D12, which is specific for HLA-E. The lymphocytes from -35 CC subjects expressed a significantly higher level of surface HLA-C when compared to those from -35 TT subjects, but this difference in HLA-C expression can be attributed primarily to the very low expression of a single allelic product, HLA-Cw*07. Increased surface HLA-C should translate to functional differences between CC and TT subjects. This study confirmed that HLA-C restricted CD8 T cell responses against HIV-1 do exist, even for HLA-Cw*07, but represent a minority of total T cell responses. They were detected in all -35 SNP genotypes but there were no functional differences, making it unlikely that the protective effect of this SNP on viral load set point could be accounted for solely by HLA-C restricted T cell responses. Finally, a viral suppression assay was used to investigate the capacity of CD8 T cells to suppress HIV-1 replication in Caucasian and African subjects. We provide evidence that the -35 SNP effect on viral load is indeed T cell mediated. However, we suggest that the protective effect of the -35 SNP on viral load set point manifests as a result of linkage disequilibrium of this polymorphism with both favourable and unfavourable HLA-B and HLA-C alleles.
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Ribeiro, Susan Pereira. « Análise da imunogenicidade de uma vacina de DNA codificando epitopos CD4 promíscuos e conservados do HIV-1 em camundongos BALB/c e transgênicos para moléculas de HLA classe II ». Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-22092010-120821/.

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Abordagens atuais no desenho de vacinas contra o HIV-1 estão focadas em imunógenos que codificam proteínas inteiras do HIV-1 e visam induzir respostas citotóxicas específicas. É concebível que vacinas bem-sucedidas devem induzir respostas contra múltiplos epitopos do HIV-1, coincidindo com seqüências das cepas circulantes do vírus, conhecido por sua grande variabilidade genética. Sabe-se que células T CD4+ são necessárias para indução de respostas efetivas de linfócitos T CD8+ citotóxicos. Neste trabalho, nós avaliamos a imunogenicidade de uma vacina de DNA codificando 18 epitopos para linfócitos T CD4+, conservados e ligadores de múltiplas moléculas HLA-DR em camundongos BALB/c e em quatro linhagens de camundongos transgênicos para moléculas de HLA classe II. Os camundongos imunizados apresentaram respostas de amplitude e magnitude significativas com proliferação e secreção de citocinas por linfócitos T CD4+ e T CD8+. Onze dos 18 epitopos para linfócitos T CD4+ presentes na vacina foram reconhecidos pelas linhagens de camundongos transgênicos para moléculas de HLA classe II. Em suma, 17 dos 18 epitopos codificados pela vacina foram reconhecidos. As células induzidas pela vacina apresentaram um perfil polifuncional com tipo 1 de citocinas, incluindo produção de IFN- , TNF- e IL-2. A vacina também induziu células T CD4+ de memória central de longa duração, capazes de fornecer auxílio contínuo para células T CD8 +. Pela capacidade da vacina HIVBr18 de induzir respostas contra múltiplos epitopos de linfócitos T CD4+ conservados que podem ser reconhecidos no contexto de múltiplas moléculas de HLA classe II, esse conceito vacinal pode solucionar o problema da variabilidade genética viral assim como aumentar a cobertura populacional. Portanto, essa vacina, pode ser útil se utilizada isoladamente ou como fonte de auxílio cognato para células T CD8+ HIV-específicas induzidas por outros imunógenos gerando resposta em uma grande proporção dos vacinados
Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that elicit cytotoxic CD8+ responses. It is conceivable that successful vaccines have to elicit responses to multiple epitopes, to match circulating strains of HIV, a virus known for its high genetic variability. It is known that CD4+ T cell responses are necessary for effective CD8+ antiviral responses. Here we assessed the immunogenicity of a DNA vaccine encoding 18 conserved, multiple HLA-DR-binding HIV CD4 epitopes in BALB/c and four strains of HLA class II-transgenic mice. Immunized mice displayed CD4+ and CD8+ proliferative and cytokine T cell responses of significant breadth and magnitude. Eleven out of the 18 encoded epitopes were recognized by CD4+ T cells from HLA class IItransgenic strain. Overall, 17 out of the 18 encoded peptides were recognized. The induced T cell response had a polyfunctional type 1 cytokine profile, including IFN- , TNF- and IL-2. The vaccine also induced long-lived central memory CD4+ T cells, which might provide sustained help for CD8+ T cells. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be usefull either as a standalone approach or as a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, eliciting responses in a wide proportion of vaccinees
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Francesca, Parolini. « HIV-1 Env and HLA-C interaction is crucial in modulating viral infectivity ». Doctoral thesis, 2018. http://hdl.handle.net/11562/979164.

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Introduction HLA-C plays a crucial role in the progression of HIV-1 infection. Host genetic HLA-C variants, appear to be associated with a different ability to control HIV-1 infection. A higher HLA-C expression is associated with a better activation of cytotoxic T lymphocytes (CTLs) and of Killer Immunoglobulin like receptors (KIR) on NK-cells, which lead to a better HIV-1 infection control. Vice-versa, a lower HLA-C expression leads to a rapid progression toward AIDS. In addition, different HLA-C alleles present different binding stabilities to β2microglobulin (β2m)/peptide. Noteworthy, some HLA-C highly expressed/protective alleles are also stably bound to β2m/peptide, while some low expressed/non-protective variants present an unstable bond to β2m/peptide. Finally virions lacking HLA-C have reduced infectivity and increased susceptibility to neutralizing antibodies. Experiments In the present work, it was first characterized the association between HLA-C and HIV-1 Env. We investigated if HIV-1 infection involves HLA-C free chains or the heterotrimeric complex, and to this purpose the A3.01 cell line and its HIV-1-infected counterpart ACH-2, as well as PM1 cells, were used as in vitro infection model. HEK-293T β2m negative cells, generated using CRISPR/Cas9 system, were used to produce HIV-1 pseudoviruses and to test their infectivity. Then, the proportion between HLA-C associated to β2m and HLA-C presents as free chains on the cell surface was characterized on PBMC from healthy donors, bearing both Stable or Unstable HLA-C alleles. In addition, PBMC were tested for their ability to support HIV-1 infection in vitro. Results HIV-1 infection induces the appearance of HLA-C free chains on the surface of infected cells, which may be responsible for the increased HIV-1 infectivity. HIV-1 Env-pseudotyped viruses produced in the absence of β2m, thus lacking HLA-C on their envelope, were less infectious than those produced in the presence of β2m. By analysing PBMC from healthy donors, differences in HLA-C heterotrimers stability and HLA-C expression levels were found. Finally, it was reported that R5 HIV-1 virions produced by PBMC having Unstable HLA-C alleles were more infectious than those produced by PBMC having the Stable variants. Conclusions The outcome of HIV-1 infection might depend both on the HLA-C surface expression levels and on HLA-C/β2m/peptide binding stability. According to this model, PBMC carrying low expressed/Unstable HLA-C alleles have a high proportion of HLA-C free chains on their surface that raises viral infectivity and, at the same time, a low proportion of HLA-C heterotrimeric complexes which leads to a poor control of HIV-1 infection, and thus to a rapid progression toward AIDS.
È noto che alcuni polimorfismi del sistema HLA giocano un ruolo cruciale nell’eziopatogenesi e nella prognosi di numerose malattie infettive, fra le quali l’AIDS (Sindrome da Immunodeficienza Acquisita). Recenti studi hanno evidenziato una forte correlazione fra i livelli di espressione di HLA-C e il controllo della replicazione del virus dell’immunodeficienza umana (HIV-1). Alti livelli di espressione sono stati correlati con un miglior controllo dell’infezione, mentre bassi livelli sono stati associati con una progressione più rapida della malattia. Inoltre, è noto che la molecola HLA-C, presente sull’envelope di HIV-1, in associazione con la glicoproteina Env, è in grado di aumentarne l’infettività. Il ruolo protettivo di alti livelli di espressione di HLA-C sembra essere in contraddizione con il ruolo dell’ HLA-C stesso nell’aumentare l’infettività virale quando incorporato nel virione. Ciò potrebbe essere dovuto alla presenza di diverse conformazioni dell’ HLA-C. È infatti noto che diverse varianti alleliche dell’HLA-C presentano una diversa stabilità di legame con la β2 microglobulina (β2m) e il peptide. In particolare, l’HLA-C può presentarsi associato alla β2m e al peptide, costituendo un complesso che svolge un ruolo chiave nell’attivazione del sistema immunitario, oppure come free chain, dissociato dal complesso. I primi risultati di questo lavoro hanno dimostrato che la proteina Env di HIV-1 è in grado di associarsi all’HLA-C quando presente nella conformazione di free chain. L’ipotesi testata nello studio prevede l’esistenza di un’associazione fra la suscettibilità all’infezione da HIV-1 e le diverse varianti alleliche di HLA-C che possono essere preferibilmente presenti o come complesso trimerico o come free chain. Individui con varianti di HLA-C aventi una forte stabilità come trimero completo mostrerebbero una maggiore immunità contro HIV-1 e una ridotta infettività virale, mentre soggetti con varianti dell’HLA-C che facilmente si dissociano dalla β2m e dal peptide mostrerebbero una ridotta risposta immunitaria nei confronti di HIV-1 e la produzione di virioni maggiormente infettivi. Nel suo complesso, questo studio fornisce nuove informazioni che potrebbero rivelarsi utili per la progettazione di nuove strategie vaccinali e approcci terapeutici contro HIV-1.
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Stefani, Chiara. « Host factors restricting HIV-1 infectivity ». Doctoral thesis, 2022. http://hdl.handle.net/11562/1073347.

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The field of host-retrovirus interactions is complex and wide since multiple cellular proteins can act as positive or negative factors for viral infections or pathogenesis. In this work, we investigated the role of some cellular proteins on HIV-1 infectivity. The first examined factor is HLA-C and its potential role in AIDS progression. The analysis of the HLA-C genotype of 96 HIV-1 positive patients unveils the statistically significant association between some HLA-C variants, less stably bound to β2microglobulin/peptide complex, and a more rapid AIDS progression (p-value = 0.0143). The second considered aspect is the role of cellular proteins on HIV-associated neurocognitive disorders development (HAND). Finding new biomarkers and genetic factors linked to HIV associated neurocognitive disorders was the aim of this second study. The analyzed factors include HLA-C, Apolipoprotein E, β2microglobulin, and Neurofilament Light Chain (NFL). A cohort of 32 patients was selected for this study and the subjects were classified according to their neurocognitive status. HLA-C and Apolipoprotein E genotypes were determined through an Allele Specific PCR approach, while β2microglobulin and Neurofilament Light Chain plasma levels were quantified. Unfortunately, an association between the analyzed genetic factors/biomarkers and HAND development could not be determined due to the poor patient’s recruitment caused by the COVID-19 pandemic. The third analyzed factor is ACOT8, a thioesterase discovered as an HIV-1 Nef protein-interacting partner. To unravel ACOT8 involvement in HIV-1 infectivity pseudotyped viruses were produced using Hek293T wild type or ACOT8 knock-out cell lines. The infection step was performed using TZM-bl wild type or TZM-bl ACOT8 knock-out cell lines. This approach revealed a probable ACOT8 role on virus production and infection that will be further analyzed.
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Serena, Michela. « HIV-1 and host cell proteins interactions : role of Env and HLA-C in viral infectivity and molecular analysis of Nef and ACOT8 association ». Doctoral thesis, 2015. http://hdl.handle.net/11562/914182.

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HIV-1, per compiere il suo ciclo infettivo, si serve dell’associazione con numerose proteine cellulari. In questo lavoro mi sono occupata di studiare l’interazione tra proteine di HIV-1 e proteine cellulari, in particolare tra Env e HLA-C e tra Nef e la tioesterasi umana (ACOT8). Studi precedenti hanno dimostrato come la presenza di HLA-C sui virioni di HIV-1 ne aumenti l’infettività; è stata inoltre riportata una correlazione tra i livelli di espressione di HLA-C e la replicazione virale. In questo studio abbiamo dimostrato che la presenza di HIV-1 aumenta la quantità di molecole HLA-C open conformer (non associate alla β2-microglobulina) sulla membrana di cellule infettate; che la proteina Env è in grado di ripristinare la presenza di HLA-C sulla superficie di cellule negative per la β2m; che HLA-C associa alternativamente o con la β2m o con Env; che Env può sostituire la β2m nel trasporto di molecole HLA-C open conformer sulla membrana cellulare; che pseudovirus di HIV-1 sono meno infettivi in presenza di β2m, suggerendo un meccanismo competitivo tra Env e β2m per il legame a HLA-C. In nostri dati suggeriscono quindi che l’aumento di infettività di HIV-1 in presenza di HLA-C è strettamente legato alla disponibilità di molecole open conformer, dimostrando come la stabilità del legame tra HLA-C e laβ2m sia un fattore discriminante per l’associazione con Env. Pertanto le differenze osservate tra i livelli di espressione in membrana tra i diversi alleli di HLA-C può essere dovuta ad una diversa affinità per il legame alla β2m. Di conseguenza la maggiore o minore stabilità di associazione con la β2m o con Env, può conferire alle diverse varianti alleliche di HLA-C una propensione per agire come molecole immuno-competenti o come molecole accessorie per HIV-1. La proteina Nef di HIV-1 interagisce con diverse proteine cellulari, tra cui ACOT8. Tale interazione può modulare la composizione dei raft lipidici durante l’infezione virale. Attualmente le regioni di Nef coinvolte nell’associazione con ACOT8 sono state identificate, ma, a causa della mancanza di dati strutturali per ACOT8, non vi è alcuna informazione riguardante le regioni di ACOT8 importanti per l’interazione con Nef. In questo lavoro, mediante l’utilizzo di metodi di predizione bioinformatica, è stata modellizzata la struttura di ACOT8 e, attraverso procedure di docking, è stata riscontrata un’alta complementarietà di carica tra le superfici di Nef e ACOT8, che ha permesso l’identificazione degli aminoacidi di ACOT8 possibilmente coinvolti nell’interazione. Tali dati sono poi stati validati attraverso esperimenti in vitro. Sono stati preparati diversi mutanti di delezione per ACOT8 e, mediante immunofluorescenza e saggi di co-immunoprecipitazione, abbiamo dimostrato come la mutazione p∆PK (K91S) sia sufficiente per compromettere l’associazione con Nef, suggerendo il coinvolgimento della Lys91 in tale interazione. Inoltre anche le regioni ∆PAK (R45-F55) e ∆PK (R86-P93) sono risultate essere importanti per il legame a Nef, indicando che più aminoacidi possono essere coinvolti nell’associazione tra le due proteine. Al contrario, in seguito alla delezione p∆PAK (K52), l’interazione con Nef è stata mantenuta, indicando come tale aminoacido non sia invece coinvolto. Tali osservazioni aprono la strada per il possibile sviluppo di molecole inibitorie volte a ridurre la funzionalità di ACOT8 e quindi comprometterne l’interazione con Nef, riducendo così l’infettività di HIV-1.
HIV-1 relies on several host cell proteins to carry out its infective cycle. In this work I investigated the interactions between HIV-1 proteins and human proteins, in particular between Env and HLA-C and between Nef and the thioesterase 8 (ACOT8). HLA-C presence on HIV-1 virions increases viral infectivity; in addition a correlation between HLA-C expression levels and HIV-1 replication control has been reported. In this study we demonstrated that: HIV-1 presence increases the amount of HLA-C open conformers (not bound to β2m) on infected cells membrane; HIV-1 Env relocates HLA-C on the cell surface of β2m-negative cells; HLA-C alternatively associates with Env or with β2m; Env replaces β2m in the transport of HLA-C open conformers to the cell surface; HIV-1 pseudoviruses are less infectious in the presence of β2m, suggesting a competitive mechanism in HLA-C binding to Env or β2m. Taken together, our data suggest that the enhanced infectivity conferred to HIV-1 by HLA-C specifically involves HLA-C molecules as open conformers. In addition this work draws attention to HLA-C stability as a discriminatory factor for the association with Env. Differences observed between HLA-C alleles may be the consequence of different binding affinities to β2m, which may account for distinct surface expression levels of HLA-C allelic variants. Differences in binding affinity to β2m or to alternative ligands such as HIV-1 Env may confer to allelic variants of HLA-C the ability to preferentially act either as a conventional immune-competent molecule or as an accessory molecule involved in HIV-1 infectivity. HIV-1 Nef interacts with several cellular proteins, among which ACOT8. This interaction may modulate lipid composition in membrane rafts during HIV-1 infection. Currently, the regions involved in the interaction have been experimentally characterized on Nef but not on ACOT8. The lack of structural information for ACOT8 hampers a deep characterization of the putative interaction regions. In this work we modelled, through in silico predictions, the ACOT8 structure in order to identify the aminoacids putatively involved in the interaction with Nef. Our data demonstrated a high charge complementarity between Nef and ACOT8 surface, which allowed the identification of the ACOT8 putative contact points involved in the interaction. The predictions were then validated by in vitro assays. Several ACOT8 deletion mutants were prepared. Through immunofluorescence and co-immunoprecipitation assays we demonstrated that the ACOT8 p∆PK mutation (K91S) is sufficient to abrogate the association with Nef, indicating that K91 plays a fundamental role for this interaction. In addition also the ACOT8 ∆PAK deletion (R45- F55), as well as the ∆PK deletion (R86-P93) resulted to be determinant for the Nef association, suggesting that other residues might be involved. No effects on Nef binding were observed upon ACOT8 p∆PAK deletion (K52) indicating that this aminoacid is not significantly involved in the interaction. Our findings open the way to further investigations for the designing of new inhibitory molecules that interfere with the Nef activity and thus reduce HIV-1 infectivity.
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Chapitres de livres sur le sujet "HIV-1, HLA-C"

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It is now clear that of fortunate circu omuste ing a first-rate scientist, Walker other parts of the global ocean also participate in the the art of statistics htaahn is work because of a confluence Southern Oscillation, manifested through changes in matical tool of the ob d se cdeesv . e F lo ir pset, shortly beforehand, sea surface temperature and the overlying atmos­ also a very ab rvational dscriaepnicdelsy . aWsaalkm er atwhaes ­ phe B ri ycctih rc e u la la ti toen. 1970s and early 1980s, climate o st fat ti hse ti cIsnd (W ian alM ker le1 99 m7a ) t . h H em av aitn ic giatn ak ewn ho understood scientists were able to document the relationships gained the oppo ertteuonrio ty lo tgoicc al Departme th netijnob19o0f3h , e h ad ehRyap sm ot uhsesso is neda nd byCaB rp je ernktneers 19 in 8 2, mwoh re odd is e c ta uisls ed (e . tgh . e , m re aqtuhierm ed ata ic a la l rg oepesrta aff capab alreryoofupteh rf is orsm tu idniges, m w an h u ic ahlT So hue th ceorunplO ed sco il cleaa ti n o -n a / tEmlosNpihneoreasvaaricao ti uopnlecdenstyrsetdemo ) n . 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Tmreonpti . caDlO ur cienagntG he lo b 1 al 98A0tsmoasnpdh er 1e99 (T 0s OGaAs ) ereix es p er o i­ flsaurfgfe ic -s ie cnatlence li amr-agtleob va arl ia d ti aotnas . to de hsccre ib n e tu raynd to agnaatlh ys eereom ur p iri ucnadl, e m rs o ta dned ll iinngg , aonfdtthheeo re p ti hcyaslicsa tu l di m es e c in hcarneiassm ed s 192 T3heansdtu1d9 ie 2s4 , bWyaW lk a e lker and others (e.g., Walker aad ss voacnicae te sdinwiutnhdEeN rs S ta O n . diAngdettealielceodndnie sc c u ti sosn io pnao tt ferrencsen in trge lo la b ti aol) nsshuirp fa s ce exp is re te s d su rbeertawnedenB li lsasrg1e9 -s 3c2a ) le s h ( o i. w e. e , d n that the TOGA era (1985-94) can be found in Trenberth patterns -in particular, tphaettIen rn d s ia n an sdum re m gional rain efaarl -l et aTl. h1e 99 i8deanntd if i A ca ll tainone ta o l. f 19 so 9m6. e of the physical v ra aitn io fa nlal. l W ev a id lk eenrc ’s erfeosreatrhcehepxrio st veindceedo th feefr monso an ir osrtgaonbisseorn ­ m rev ec it h a anism ed conne l c is t e io dnsi nt aesrseosct iated with patterns. in A W se a ri lekser’ osENfp SO has st ruedciiepsi ta w ti i o th n g re te alte ly -glo more wHoerbcaal-ls le cda le tpk did no hi tsattthee rn hav Soofuitnh terannual climate variability. complete data sets (e.g., Kiladis and Diaz 1989 ; expected because, efotrhe re a im e p rn acOt scillatio sons th tahtartemma ig n. htI in unh itia nc alveel ly ar b , e h th einsrReocpoenlfeiw rm sk eida se nvde ra Hlao lp f e th rt et1e9 le 8c6o , nn 1e9c8t7 io , ns ansdu gg 1e9s9 te 2 d ) c so o o rr n e la ptr io ec nispib ta et t w io enenwtehaekepnreed ss uarbeopuatt te th rn esta im nd e m th oene ­ cboynW ne acltkieornsa . ndRootphee le rs w , saknidaindde nt H ifi aeldpeardt di ( t 1 io 9n8a7ltaen le-were discovered. Th y 1989) attempted to improve the usefulness of tele d ­ taitmtehemomsitdodf le thoefetah rl eec tw or ernetliae ti tohncsesnttruernyg , th beuntebdyag th a a in tcdooncnuemce ti notn patterns y work ha ing regions foorfstehaesognlaolbcelitm ha att , eipnreaddidcittiioonnb to y fille Adc in ru c w ia alspaap rt hyosfictahleepxipcltaunrdebteheantfro em rg aoitn ten atio ed . to be a m ls e o re lhyadshroew la itn io gnssh ta itp is stiw ca ilthEN EN SO SO -p rtehca ip t it w at eiroenhliignhklsy , t te hleecSoonuntehcetrinonOp sc aitltleartn io s. n A ju rsetvaisewaonfk fo nrow th leedogbesaeb rv oeudticdoennstiisftieendttfhreom se aespoin so sdaend to reegpiiosn od seo . f T th h e ey g p lo a b rt eicw ul haerr ly physical explanation precipitation was associated with ENSO in at least 75 e ». Dans Droughts, 56. Routledge, 2016. http://dx.doi.org/10.4324/9781315830896-39.

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Actes de conférences sur le sujet "HIV-1, HLA-C"

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Santos, André Luiz Dos. « EXAMES IMUNOGENÉTICOS PARA AVALIAÇÃO DE COMPATIBILIDADE RECEPTOR-DOADOR EM TRANSPLANTES EM SUMA ». Dans II Congresso Brasileiro de Biologia Molecular On-line. Revista Multidisciplinar em Saúde, 2021. http://dx.doi.org/10.51161/rems/2335.

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Introdução: Transplantes são processos onde a compatibilidade Receptor-Doador é fundamental para evitar-se a perda do paciente ou do órgão, que poderia ser melhor transplantado. Para isso, realizam-se múltiplos testes, principalmente clínicos e laboratoriais, avaliando ambos pacientes, buscando sucesso dos transplantes. Objetivo: Reconhecer a importância dos exames imunogenéticos para compatibilidade Receptor-Doador. Material e Métodos: Pesquisa descritiva em documentos científicos em português, no limite de dez anos, no Google Acadêmico e Scielo, destacando os termos: transplantes, imunogenética, rejeição, compatibilidade, combinados entre si, pareando-os. Resultados foram obtidos de um total de sete artigos. Resultados: As avaliações devem considerar a ausência de: (a) contraindicações absolutas - Sorológicas HIV, HTLV I e II, Hepatites B e C; Infecções virais; HIV; Meningoencefalite herpética; Linfoma-leucemia de Células T; Doença por Príons; Neoplasia maligna ativa; Lúpus; Artrite Reumatoide; Esclerodermia e Uso de Drogas. (b) contraindicações relativas - malignidade extra-hepática; SIDA doença e hipertensão pulmonar. (c) contraindicações clinicas - Tumores ativos, infecções não resolvidas (exceto para HIV, HCV, HBV, mas devem ser controlados); rejeição do paciente e expectativa de vida baixa; pacientes desnutridos; pessoas com transtornos mentais ou instabilidade emocional; pessoas que abusam de álcool, tabaco ou outras drogas; (d) contraindicações laboratoriais - Pacientes com doenças e infecções hepáticas e cardiovasculares não controladas. A identidade HLA consiste em vários genes agrupados numa mesma região do cromossomo 6. Sabe-se que mais de 11.000 alelos foram identificados, portanto, é raro que duas pessoas tenham o mesmo conjunto de genes. Porém, mesmo com o uso de imunossupressores para auxiliar o sistema imunológico a se adaptar ao ataque desse corpo estranho, pode ocorrer rejeição do órgão. Os principais exames que inferem contra-indicações são: (a) Tipagem HLA de receptores de transplante de células-tronco hematopoiéticas; (b) Tipagem HLA de doadores de células-tronco hematopoiéticas relevantes; (c) Tipagem HLA de doadores voluntários de células-tronco hematopoiéticas - Fase 1. Busca-se indicadores a presença, no soro do receptor, de anticorpos contra antígenos HLA do doador e identificação de genes HLA classe I e II. Conclusão: Entre as formas de avaliação de contra-indicações para recepção de tecidos, a avaliação laboratorial imunogenética é a mais importante, pois é nela que se saberá a compatibilidade Receptor-Doador.
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Preussner, Brian D., Joseph A. Nenni et Vondell J. Balls. « An Overview of Risk Management Planning for Hot-Isostatic Pressure Treatment of High-Level Waste Calcine for the Idaho Cleanup Project ». Dans ASME 2012 Pressure Vessels and Piping Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/pvp2012-78150.

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The Calcine Disposition Project (CDP) of the Idaho Cleanup Project (ICP) has the responsibility to retrieve, treat, and dispose of the calcine stored at the Idaho Nuclear Technology and Engineering Center (INTEC) located at the Idaho National Laboratory. Calcine is the granular product of thermally treating, or calcining liquid high-level waste (HLW) that was produced at INTEC during the reprocessing of spent nuclear fuel (SNF) to recover uranium. The CDP is currently designing the Hot Isostatic Pressure (HIP) treatment for the calcine to provide monolithic, glass-ceramic waste form suitable for transport and disposition outside of Idaho by 2035 in compliance with the Idaho Settlement Agreement. The HIP process has been used by industry since its invention, by Battelle Institute, in 1955. Hot isostatic pressing can be used for upgrading castings, densifying pre-sintered components, and consolidate powders. It involves the simultaneous application of a high pressure and temperature in a specially constructed vessel. The pressure is applied on all sides with a gas (usually inert) and, so, is isostatic. The CDP will use this treatment process (10,000 psi at 1,150 C) to combine physically and chemically a mixture of calcine and granular additives into a non leachable waste-form. The HIP process for calcine involves filling a metal can with calcine and additives, heating and evacuating the can to remove volatiles, sealing the can under vacuum, and placing the can within the HIP machine for treatment. Although the HIP process has been in use for over 50 years it has not been applied in large scale radioactive service. Challenges with retrofitting such a system for Calcine treatment include 1) filling and sealing the HIP can cleanly and remotely, 2) remotely loading and unloading the HIP machine, and 3) performing maintenance and repair on a 300 ton, hydraulically actuated machine in a highly radioactive hot cell environment. In this article, a systems engineering approach, including use of industry-proven design-for-quality tools and quantitative assessment techniques is summarized. Discussions on how these techniques were used to improve high-consequence risk management and more effectively apply failure mode, RAMI, and time and motion analyses at the earliest possible stages of design are provided.
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Sayenko, Sergey Yu, G. A. Kholomeyev, B. A. Shilyaev, A. V. Pilipenko, E. P. Shevyakova, R. V. Tarasov et S. V. Gabelkov. « Preparing the Spent Nuclear Fuel for Long-Term Storage and Final Disposal by Encapsulating It Into Glass-Ceramic Waste Forms ». Dans ASME 2001 8th International Conference on Radioactive Waste Management and Environmental Remediation. American Society of Mechanical Engineers, 2001. http://dx.doi.org/10.1115/icem2001-1212.

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Abstract This paper describes the research work carried out at the NSC KIPT to develop and apply a final waste form in the shape of a monolithic solid block for the containment of spent nuclear fuel. To prepare radioactive waste for long-term storage and final deep geological disposal, investigations into the development of methods of immobilizing HLW simulators in protective solid matrices are being conducted at the NSC KIPT. For RBMK spent nuclear fuel it is proposed and justified to encapsulate the spent fuel bundles into monolithic protective blocks, produced with the help of hot isostatic pressing (HIP) of powder materials. In accordance with this approach, as a material for the protective block made up of the glass-ceramic composition prepared by sintering at isostatic pressure, the powder mixture of such natural rocks as granite and clay has been chosen. Concept approach and characterization of waste form, technological operations of manufacturing and performance assessment are presented. The container with spent fuel for long-term storage and final disposal presents a three barrier protective system: ceramic fuel UO2 in cladding tube, material of the glass-ceramic block, material of the sealed metal capsule. Investigations showed that the produced glass-ceramic material is characterized by high stability of chemical and phase compositions, high resistance in water medium, low porosity (compared with the porosity of natural basalt). With the help of mathematical calculations it was shown that the absorbed dose of immobilizing material by RBMK spent fuel irradiation for 1000 years of storage in the geological disposal after 10 years of preliminary cooling will be ∼ 3.108 Gy, that is 2–3 orders of magnitude less than the values corresponding to preserving radiation resistance and functional parameters of glasses and ceramics. The average value of velocity of linear corrosion in water medium of the protective layer made up of the glass-ceramic composition determined experimentally makes up ∼ 15 mm per year. This allows to use glass-ceramic compositions effectively as an engineering barrier in the system of spent fuel geological disposal and to increase the lifetime of the waste container, in particular, up to 3000 years with the layer thickness ∼ 40 mm. The possible release of radionuclides from the waste container during its interim storage in the open air (near-surface storage) is estimated. The calculations are made by taking into account the possible increase of coefficients of radionuclide diffusion from 10−16 to 10−14 m2/c as a result of spent fuel radiation affecting the protective layer. The obtained results showed that the protective barrier (about 40 mm) at the base of the glass-ceramic composition, ensures reliable isolation from the environment against the release of radionuclides from the controlled near-surface long-term storage far up to 1000 years. The relatively limited release of radionuclides will make up about 1% for the period of more than 400 years, and 10% - in 1000 years. During this period of time, the radionuclides 90Sr and 137Cs will completely turn into stable 90Zr and 137Ba and the decay of many transuranium elements will occur. The results from laboratory scale experiments, tests and calculations carried out so far, show that the proposed glass-ceramic materials may be used as basic materials for manufacturing the monolithic protective block in which the spent fuel elements will be embedded with the aim of further long-term storage or final disposal.
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