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Добірка наукової літератури з теми "HIV-1 HLA-C AIDS"

Автор: Grafiati

Опубліковано: 11 березня 2023

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Статті в журналах з теми "HIV-1 HLA-C AIDS"

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 (November 27, 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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Murakoshi, Hayato, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, et al. "Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes." Journal of Virology 89, no. 10 (March 4, 2015): 5330–39. http://dx.doi.org/10.1128/jvi.00020-15.

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ABSTRACTIdentification and characterization of CD8+T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8+T cells have been only partially identified. In this study, we sought to identify CD8+T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8+T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P= 2.2 × 10−11) and positively associated with CD4 count (P= 1.2 × 10−11), indicating strong synergistic effects of these T cells on HIV-1 controlin vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8+T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes.IMPORTANCEHLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52:01-restricted and 3 HLA-B*67:01-restricted CTLs, suggesting that these CTLs play a predominant role in HIV-1 control. The 13 CTLs showed synergistic effects on HIV-1 control. Twelve out of these 13 epitopes were recognized as conserved or cross-recognized ones. These findings strongly suggest that these 12 epitopes are candidates for antigens for AIDS vaccines.

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Yindom, Louis-Marie, Aleksandra Leligdowicz, Maureen P. Martin, Xiaojiang Gao, Ying Qi, Syed M. A. Zaman, Maarten Schim van der Loeff, et al. "Influence of HLA Class I and HLA-KIR Compound Genotypes on HIV-2 Infection and Markers of Disease Progression in a Manjako Community in West Africa." Journal of Virology 84, no. 16 (June 2, 2010): 8202–8. http://dx.doi.org/10.1128/jvi.00116-10.

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ABSTRACT Overall, the time to AIDS after HIV-2 infection is longer than with HIV-1, and many individuals infected with HIV-2 virus remain healthy throughout their lives. Multiple HLA and KIR gene products have been implicated in the control of HIV-1, but the effect of variation at these loci on HIV-2 disease is unknown. We show here for the first time that HLA-B*1503 is associated significantly with poor prognosis after HIV-2 infection and that HLA-B*0801 is associated with susceptibility to infection. Interestingly, previous data indicate that HLA-B*1503 is associated with low viral loads in HIV-1 clade B infection but has no significant effect on viral load in clade C infection. In general, alleles strongly associated with HIV-1 disease showed no effect in HIV-2 disease. These data emphasize the unique nature of the effects of HLA and HLA/KIR combinations on HIV-2 immune responses relative to HIV-1, which could be related to their distinct clinical course.

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Lazaryan, Aleksandr, Elena Lobashevsky, Joseph Mulenga, Etienne Karita, Susan Allen, Jianming Tang, and Richard A. Kaslow. "Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans." Journal of Virology 80, no. 12 (June 15, 2006): 6056–60. http://dx.doi.org/10.1128/jvi.02119-05.

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ABSTRACT Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties. We examined alleles of the HLA-B58 supertype (B58s) in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-seropositive Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P = 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P = 0.02) or B*5802-Cw*0602 (P = 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P = 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802 with slow (P = 0.06) and rapid (P = 0.003) disease progression, respectively. In neither population were B*1516-B*1517 alleles associated with more favorable responses. Overall, B58s alleles, individually or as part of an HLA-B-HLA-C haplotype, appeared to have a distinctive impact on HIV-1 infection among native Africans. As presently defined, B58s alleles cannot be considered uniformly protective against HIV/AIDS in every population.

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Mori, Masahiko, Ellen Leitman, Bruce Walker, Thumbi Ndung’u, Mary Carrington, and Philip Goulder. "Impact of HLA Allele-KIR Pairs on HIV Clinical Outcome in South Africa." Journal of Infectious Diseases 219, no. 9 (December 28, 2018): 1456–63. http://dx.doi.org/10.1093/infdis/jiy692.

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Abstract Background HLA class I contributes to HIV immune control through antigen presentation to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. In contrast to investigations of CTL, studies of NK cells in HIV control through HLA-killer immunoglobulin-like receptor (KIR) interactions remain sparse in African cohorts. Methods Treatment-naive, chronically HIV-infected adults (N = 312) were recruited from South Africa, and the effects of HLA-KIR pairs on clinical outcome were analyzed. Results There was no significant difference in viral load among all subjects with HLA alleles from the HLA-C1 group (P = .1). However, differences in HLA-C type significantly influenced viremia among 247 KIR2DL3 positives (P = .04), suggesting that specific HLA-KIR interactions contribute to immune control. Higher viral load (P = .02) and lower CD4+ T-cell counts (P = .008) were observed in subjects with HLA-C*16:01+KIR2DL3+. Longitudinal analysis showed more rapid progression to AIDS among HLA-C*16:01+KIR2DL3+ subjects (adjusted hazard ratio 1.9, P = .03) than those without this genotype, independent of CD4+ T-cell count and viral load. Conclusions These results highlight the existence of unique anti-HIV innate immunity within distinct populations and the contribution of KIR on NK cells and some CTLs to the well-described HLA-mediated impact on HIV disease progression.

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Celsi, Fulvio, Eulalia Catamo, Giulio Kleiner, Paola Maura Tricarico, Josef Vuch, and Sergio Crovella. "HLA-G/C, miRNAs, and Their Role in HIV Infection and Replication." BioMed Research International 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/693643.

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In recent years, a number of different mechanisms regulating gene expressions, either in normal or in pathological conditions, have been discovered. This review aims to highlight some of the regulatory pathways involved during the HIV-1 infection and disease progression, focusing on the novel discovered microRNAs (miRNAs) and their relation with immune system’s agents. Human leukocyte antigen (HLA) family of proteins plays a key role because it is a crucial modulator of the immune response; here we will examine recent findings, centering especially on HLA-C and -G, novel players lately discovered to engage in modulation of immune system. We hope to provide novel perspectives useful to find out original therapeutic roads against HIV-1 infection and AIDS progression.

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Abitew, Abaineh Munshea, Ranbir Chander Sobti, Vijay Lakshmi Sharma, and Ajay Wanchu. "Analysis of transporter associated with antigen presentation (TAP) genes polymorphisms with HIV-1 infection." Molecular and Cellular Biochemistry 464, no. 1-2 (November 16, 2019): 65–71. http://dx.doi.org/10.1007/s11010-019-03649-x.

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AbstractHuman leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR–RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06–1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56–7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case–control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.

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Novitsky, V., P. Gilbert, T. Peter, M. F. McLane, S. Gaolekwe, N. Rybak, I. Thior, et al. "Association between Virus-Specific T-Cell Responses and Plasma Viral Load in Human Immunodeficiency Virus Type 1 Subtype C Infection." Journal of Virology 77, no. 2 (January 15, 2003): 882–90. http://dx.doi.org/10.1128/jvi.77.2.882-890.2003.

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ABSTRACT Virus-specific T-cell immune responses are important in restraint of human immunodeficiency virus type 1 (HIV-1) replication and control of disease. Plasma viral load is a key determinant of disease progression and infectiousness in HIV infection. Although HIV-1 subtype C (HIV-1C) is the predominant virus in the AIDS epidemic worldwide, the relationship between HIV-1C-specific T-cell immune responses and plasma viral load has not been elucidated. In the present study we address (i) the association between the level of plasma viral load and virus-specific immune responses to different HIV-1C proteins and their subregions and (ii) the specifics of correlation between plasma viral load and T-cell responses within the major histocompatibility complex (MHC) class I HLA supertypes. Virus-specific immune responses in the natural course of HIV-1C infection were analyzed in the gamma interferon (IFN-γ)-enzyme-linked immunospot assay by using synthetic overlapping peptides corresponding to the HIV-1C consensus sequence. For Gag p24, a correlation was seen between better T-cell responses and lower plasma viral load. For Nef, an opposite trend was observed where a higher T-cell response was more likely to be associated with a higher viral load. At the level of the HLA supertypes, a lower viral load was associated with higher T-cell responses to Gag p24 within the HLA A2, A24, B27, and B58 supertypes, in contrast to the absence of such a correlation within the HLA B44 supertype. The present study demonstrated differential correlations (or trends to correlation) in various HIV-1C proteins, suggesting (i) an important role of the HIV-1C Gag p24-specific immune responses in control of viremia and (ii) more rapid viral escape from immune responses to Nef with no restraint of plasma viral load. Correlations between the level of IFN-γ-secreting T cells and viral load within the MHC class I HLA supertypes should be considered in HIV vaccine design and efficacy trials.

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Rechavi, G., I. Ben-Bassat, M. Berkowicz, U. Martinowitz, F. Brok-Simoni, Y. Neumann, A. Vansover, T. Gotlieb-Stematsky, and B. Ramot. "Molecular analysis of Burkitt's leukemia in two hemophilic brothers with AIDS." Blood 70, no. 6 (December 1, 1987): 1713–17. http://dx.doi.org/10.1182/blood.v70.6.1713.1713.

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Abstract In two hemophilic brothers infected by the human immunodeficiency virus (HIV), Burkitt's leukemia developed within 1 year. Both patients were treated by aggressive chemotherapy, and both are still in complete remission for 23 and 14 months, respectively. Sera from both brothers contained anti-HIV antibodies. However, DNA extracted from the tumor cells, when analyzed by Southern blot using a cloned HIV probe, did not reveal HIV-related sequences. Hybridization experiments with an Epstein- Barr virus (EBV) probe revealed the presence of EBV-specific sequences in the tumors' DNA. In both patients' tumors rearranged c-myc genes were found. The rearrangements occurred in both genes 3′ to the third exon of c-myc, thereby suggesting that a variant chromosomal translocation took place in both cases. Indeed, karyotype analysis of the malignant cells of one of the patients revealed the variant t(2:8) translocation. In contrast to the majority of Burkitt's tumors carrying this translocation, which are kappa light-chain producers, cells of our patient expressed lambda chains. Furthermore, in both cases the lymphoblasts carried IgG on the surface, again an unusual finding in Burkitt's tumors. Finally, because both patients had an identical HLA phenotype, the role of genetic factors in the development of such tumors should be considered.

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In two hemophilic brothers infected by the human immunodeficiency virus (HIV), Burkitt's leukemia developed within 1 year. Both patients were treated by aggressive chemotherapy, and both are still in complete remission for 23 and 14 months, respectively. Sera from both brothers contained anti-HIV antibodies. However, DNA extracted from the tumor cells, when analyzed by Southern blot using a cloned HIV probe, did not reveal HIV-related sequences. Hybridization experiments with an Epstein- Barr virus (EBV) probe revealed the presence of EBV-specific sequences in the tumors' DNA. In both patients' tumors rearranged c-myc genes were found. The rearrangements occurred in both genes 3′ to the third exon of c-myc, thereby suggesting that a variant chromosomal translocation took place in both cases. Indeed, karyotype analysis of the malignant cells of one of the patients revealed the variant t(2:8) translocation. In contrast to the majority of Burkitt's tumors carrying this translocation, which are kappa light-chain producers, cells of our patient expressed lambda chains. Furthermore, in both cases the lymphoblasts carried IgG on the surface, again an unusual finding in Burkitt's tumors. Finally, because both patients had an identical HLA phenotype, the role of genetic factors in the development of such tumors should be considered.

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Більше джерел

Дисертації з теми "HIV-1 HLA-C AIDS"

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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Частини книг з теми "HIV-1 HLA-C AIDS"

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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." In Droughts, 56. Routledge, 2016. http://dx.doi.org/10.4324/9781315830896-39.

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