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BackgroundInterleukin-17-producing CD4 T cells contribute to the control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to Mtb is incompletely defined.MethodsWe performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context.ResultsWe identified two subsets of Th17 cells: subset 1 defined as CD4+Vα7.2-CD161+CD26+and subset 2 defined as CD4+Vα7.2-CCR6+CXCR3-cells of which subset 1 was significantly reduced in latent tuberculosis infection (LTBI) with HIV-ART, yet Mtb-responsive IL-17-producing CD4 T cells were preserved; we found that IL-17-producing CD4 T cells dominate the response to Mtb antigen but not cytomegalovirus (CMV) antigen or staphylococcal enterotoxin B (SEB), and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17-cell frequencies.ConclusionsWe found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL-17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity.

Context: Flaviviruses cause severe encephalitic or hemorrhagic diseases in humans. Its members, Kyasanur forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (ALKV), cause hemorrhagic fever and are prevalent in India and Saudi Arabia, respectively, while the tick-borne encephalitis virus (TBEV) causes a dangerous encephalitic infection in Europe and Asia. However, little information is available about the targets of immune responses for these deadly viruses. Here, we predict potential antigenic peptide epitopes of viral envelope protein for inducing a cell-mediated and humoral immune response. Methods: Using the Immune Epitope Database and Analysis Resource (IEDB-AR), we identified 13 MHC-I and two MHC-II dominant conserved epitopes in KFDV and ALKV and six MHC-I and three MHC-II epitopes in TBEV envelope proteins. Parallelly, we also predicted B-cell linear and discontinuous envelope protein epitopes for these viruses. Interestingly, the epitopes are conserved in all three viral envelope proteins. Further, the discontinuous epitopes are structurally compared with the available DENV, ZIKV, WNV, TBEV, and LIV envelope protein antibody structures. Overall structural comparison analyses highlight (i) lateral ridge epitope in the ED-III domain of E protein, and (ii) envelope dimer epitope (EDE) could be targeted for developing potent vaccine candidates as well as therapeutic antibody production. Moreover, existing structural and biochemical functions of the same epitopes in homologous viruses are predicted to have a reduced antibody-dependent enhancement (ADE) effect on flaviviral infection. [ABSTRACT FROM AUTHOR]

BackgroundInterleukin-17–producing CD4 T cells contribute to the control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to Mtb is incompletely defined.MethodsWe performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context.ResultsWe identified two subsets of Th17 cells: subset 1 defined as CD4+Vα7.2−CD161+CD26+and subset 2 defined as CD4+Vα7.2−CCR6+CXCR3−cells of which subset 1 was significantly reduced in latent tuberculosis infection (LTBI) with HIV-ART, yet Mtb-responsive IL-17–producing CD4 T cells were preserved; we found that IL-17–producing CD4 T cells dominate the response to Mtb antigen but not cytomegalovirus (CMV) antigen or staphylococcal enterotoxin B (SEB), and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17-cell frequencies.ConclusionsWe found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL-17–producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity.

Introduction: Perinatal HIV infection has decreased adverse bone health effects and mineral accrual. HIV-infected patients have a multifactorial origin, including HIV bone cell infections, inflammatory cytokine effects on osteoblast and osteoclast activity, and HAART. The research objective was to analyze the correlation between the mandibular bone density with CD4 T-cells and duration of HAART in HIV-infected children. Methods: The mandibular bone density in the HIV-infected pediatric population was evaluated using a panoramic radiograph. The research design was a cross-sectional and univariate regression analysis for the sampling method. Mandibular density analysis using Spearman and Pearson correlation and HAART duration using Kendall correlation. Thirty-five HIV-infected children and seventeen non-HIV-infected children were recruited. Results: This study showed the significant correlation between Mandibular cortical shape index of HIV-infected and non-HIV children and there is a significant correlation between fractal dimension of HIV-infected and non-HIV children (p

Background. Red rose extract is known to have anti-inflammatory and immune-modulation effects. In this study, the red rose extract was tested on CD4+T lymphocytes in vitro, and cytokine response was evaluated. Materials and Methods. The red rose (Rosa Rosaceae - Pierre de Ronsard) extract used in this study was prepared and stored at -20° C until use. CD4+T-cells were seeded in 96-well plates at 313,500 cells/well in 100μ l cell culture medium in duplicate. One-half of the wells were used for biomarker screening in the culture medium, and the other half was used for cytotoxicity assay. Twenty-four hours after plating, the cells were treated in duplicate with 100μ l of the red rose extract diluted at 0.5%, 0.1%, 0.05%, 0.01% and 0.005% (v/v) in the cell culture medium or with culture medium only as control for 72 hours. Some other wells were allocated for untreated cells, and cells treated with the rose extract at 0.005% for 48-h incubation time. Results. Several cytokines (GRO; IFN-γ; IL-1α, 6, 10; MCP-1; RANTES; TGF-β1; TIMP 1, 2; Ang1, Ang2; G-CSF; MMP-9; and VEGF R2) were elevated. Except for MMP-9, which had fold changes > 2, other cytokines were minimally elevated at various concentrations and timing of rose extract treatment. None of the mentioned cytokines were less than 0.8-fold after treatment with the rose extract. Cytotoxicity assay revealed insignificant changes in the viability of T-cells. Conclusions. There was a mild elevation in few inflammatory markers by CD4+ T-lymphocytes after in vitro treatment with the red rose extract (Rosa Rosacea - Pierre De Ronsard). Further in vitro and in vivo studies are required to evaluate the benefits of the red rose extract in immune regulation.

The immune system is the body's defense system against infection, pathogenic organisms, or foreign bodies. Human immunodeficiency virus (HIV) infection significantly reduces the number of cells involved in the immune system making the infected person prone to a greater number of infections like tuberculosis (TB). HIV infection reduces the CD4 T helper cell count and further replicates within the body. HIV-TB is a major health concern as there is more chance of progression to acquired immunodeficiency syndrome (AIDS) and the emergence of drug-resistant TB. In this case report, we see how the HIV-TB infection affects the body, significantly affecting the morbidity and mortality of the patient., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Karnan et al.)

Abstract Background Eradication of minimal residual disease (MRD), at the end of Fludarabine-Cyclophosphamide-Rituximab (FCR) treatment, is a validated surrogate marker for progression-free and overall survival in chronic lymphocytic leukaemia. But such deep responses are also associated with severe immuno-depletion, leading to infections and the development of secondary cancers. Methods We assessed, blood MRD and normal immune cell levels at the end of treatment, in 162 first-line FCR patients, and analysed survival and adverse event. Results Multivariate Landmark analysis 3 months after FCR completion identified unmutated IGHV status (HR, 2.03, p = 0.043), the level of MRD reached (intermediate versus low, HR, 2.43, p = 0.002; high versus low, HR, 4.56, p = 0.002) and CD4 > 200/mm3 (HR, 3.30, p

Background: Interleukin-17-producing CD4 T cells contribute to the control of Mycobacterium tuberculosis ( Mtb ) infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to Mtb is incompletely defined., Methods: We performed high-definition characterization of circulating Mtb -specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context., Results: We identified two subsets of Th17 cells: subset 1 defined as CD4 + Vα7.2 - CD161 + CD26 + and subset 2 defined as CD4 + Vα7.2 - CCR6 + CXCR3 - cells of which subset 1 was significantly reduced in latent tuberculosis infection (LTBI) with HIV-ART, yet Mtb -responsive IL-17-producing CD4 T cells were preserved; we found that IL-17-producing CD4 T cells dominate the response to Mtb antigen but not cytomegalovirus (CMV) antigen or staphylococcal enterotoxin B (SEB), and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17-cell frequencies., Conclusions: We found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL-17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ogongo, Tran, Marzan, Gingrich, Krone, Aweeka, Lindestam Arlehamn, Martin, Deeks, Hunt and Ernst.)

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

Minor histocompatibility antigens are the main targets of donor-derived T-cells after allogeneic stem cell transplantation. Identification of these antigens and understanding their biology are a key requisite for more insight into how graft vs. leukemia effect and graft vs. host disease could be separated. We here identified four new HLA class II-restricted minor histocompatibility antigens using whole genome association scanning. For one of the new antigens, i.e., LB-PIP4K2A-1S, we measured strong T-cell recognition of the donor variant PIP4K2A-1N when pulsed as exogenous peptide, while the endogenously expressed variant in donor EBV-B cells was not recognized. We showed that lack of T-cell recognition was caused by intracellular cleavage by a protease named asparagine endopeptidase (AEP). Furthermore, microarray gene expression analysis showed that PIP4K2A and AEP are both ubiquitously expressed in a wide variety of healthy tissues, but that expression levels of AEP were lower in primary acute myeloid leukemia (AML). In line with that, we confirmed low activity of AEP in AML cells and demonstrated that HLA-DRB1*03:01 positive primary AML expressing LB-PIP4K2A-1S or its donor variant PIP4K2A-1N were both recognized by specific T-cells. In conclusion, LB-PIP4K2A-1S not only represents a novel minor histocompatibility antigen but also provides evidence that donor T-cells after allogeneic stem cell transplantation can target the autologous allelic variant as leukemia-associated antigen. Furthermore, it demonstrates that endopeptidases can play a role in cell type-specific intracellular processing and presentation of HLA class II-restricted antigens, which may be explored in future immunotherapy of AML.

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and

Minor histocompatibility antigens are the main targets of donor-derived T-cells after allogeneic stem cell transplantation. Identification of these antigens and understanding their biology are a key requisite for more insight into how graft vs. leukemia effect and graft vs. host disease could be separated. We here identified four new HLA class II-restricted minor histocompatibility antigens using whole genome association scanning. For one of the new antigens, i.e., LB-PIP4K2A-1S, we measured strong T-cell recognition of the donor variant PIP4K2A-1N when pulsed as exogenous peptide, while the endogenously expressed variant in donor EBV-B cells was not recognized. We showed that lack of T-cell recognition was caused by intracellular cleavage by a protease named asparagine endopeptidase (AEP). Furthermore, microarray gene expression analysis showed that PIP4K2A and AEP are both ubiquitously expressed in a wide variety of healthy tissues, but that expression levels of AEP were lower in primary acute myeloid leukemia (AML). In line with that, we confirmed low activity of AEP in AML cells and demonstrated that HLA-DRB1*03:01 positive primary AML expressing LB-PIP4K2A-1S or its donor variant PIP4K2A-1N were both recognized by specific T-cells. In conclusion, LB-PIP4K2A-1S not only represents a novel minor histocompatibility antigen but also provides evidence that donor T-cells after allogeneic stem cell transplantation can target the autologous allelic variant as leukemia-associated antigen. Furthermore, it demonstrates that endopeptidases can play a role in cell type-specific intracellular processing and presentation of HLA class II-restricted antigens, which may be explored in future immunotherapy of AML. [ABSTRACT FROM AUTHOR]

• Latent tuberculosis infection (LTBI) screening was performed in only 65.5% of newly diagnosed HIV-infected patients. • LTBI tests were mainly requested for patients born outside Italy. • The majority of the LTBI subjects came from countries with a high TB prevalence. • New guidelines are needed to support LTBI screening. The Italian Society of Infectious and Tropical Diseases performed a survey on the application of guidelines for the management of persons living with HIV (PLWH), to evaluate current practice and the yield of screening for latent tuberculosis infection (LTBI) in newly-diagnosed PLWH; in addition, the offer of preventive therapy to LTBI individuals and the completion rate were analysed. Newly-diagnosed PLWH in nine centres were evaluated retrospectively (2016/2017) using binary and multinomial logistic regression to identify factors associated with LTBI diagnostic screening and QuantiFERON (QFT) results. Of 801 patients evaluated, 774 were studied after excluding active TB. LTBI tests were performed in 65.5%. Prescription of an LTBI test was associated with being foreign-born (odds ratio (OR) 3.19, p < 0.001), older (for 10-year increments, OR 1.22, p = 0.034), and having a CD4 count <100 cells/mm3 vs ≥500 cells/mm3 (OR 2.30, p = 0.044). LTBI was diagnosed in 6.5% of 495 patients evaluated by QFT. Positive results were associated with being foreign-born (relative risk ratio (RRR) 30.82, p < 0.001), older (for 10-year increments, RRR 1.78, p = 0.003), and having a high CD4 count (for 100 cells/mm3 increments, RRR 1.26, p < 0.003). Sixteen LTBI individuals started TB preventive therapy and eight completed it. LTBI screening is inconsistently performed in newly-diagnosed PLWH. Furthermore, TB preventive therapy is not offered to all LTBI individuals and compliance is poor. [ABSTRACT FROM AUTHOR]

Background: HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1) expression would specifically inhibit HIV-1 replication. Results: We designed three short interfering RNA ( siRNA) molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. Conclusion: These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4+ T-cells producing IFN-γ+ with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4+ T-cells producing: (i) IFN-γ+, (ii) TNF-α+, (iii) TNF-α+IFN-γ+, and (iv) IFN-γ+ and/or TNF-α+. The percentage of CD27− within all CD4+ T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4+ T-cells over MFI of CD27 in IFN-γ+CD4+ T-cells), being significantly increased during disease (p < 0.0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4+ T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0.91) were achieved for: (i) CD27 within IFN-γ+TNF-α+CD4+ T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γ+CD4+ T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γ+TNF-α+CD4+ T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0.77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease.

Background: Ageing can be classified in two different ways, chronological ageing and biological ageing. While chronological age is a measure of the time that has passed since birth, biological (also known as transcriptomic) ageing is defined by how time and the environment affect an individual in comparison to other individuals of the same chronological age. Recent research studies have shown that transcriptomic age is associated with certain genes, and that each of those genes has an effect size. Using these effect sizes we can calculate the transcriptomic age of an individual from their age-associated gene expression levels. The limitation of this approach is that it does not consider how these changes in gene expression affect the metabolism of individuals and hence their observable cellular phenotype. Results: We propose a method based on poly-omic constraint-based models and machine learning in order to further the understanding of transcriptomic ageing. We use normalised CD4 T-cell gene expression data from peripheral blood mononuclear cells in 499 healthy individuals to create individual metabolic models. These models are then combined with a transcriptomic age predictor and chronological age to provide new insights into the differences between transcriptomic and chronological ageing. As a result, we propose a novel metabolic age predictor. Conclusions: We show that our poly-omic predictors provide a more detailed analysis of transcriptomic ageing compared to gene-based approaches, and represent a basis for furthering our knowledge of the ageing mechanisms in human cells. [ABSTRACT FROM AUTHOR]

T-cell-mediated immune responses play a fundamental role in controlling Mycobacterium tuberculosis (M. tuberculosis) infection, and traditionally, this response is thought to be mediated by Th1-type CD4+ T-cells secreting IFN-γ. While studying the function and specificity of M. tuberculosis-reactive CD4+ T-cells in more detail at the single cell level; however, we found a human CD4+ T-cell population with a naive phenotype that interestingly was capable of producing multiple cytokines (TCNP cells). CD4+ TCNP cells phenotyped as CD95lo CD28int CD49dhi CXCR3hi and showed a broad distribution of T cell receptor Vβ segments. They rapidly secreted multiple cytokines in response to different M. tuberculosis antigens, their frequency was increased during active disease, but was comparable to latent tuberculosis infection in treated TB patients. These results identify a novel human CD4+ T-cell subset involved in the human immune response to mycobacteria, which is present in active TB patients’ blood. These results significantly expand our understanding of the immune response in infectious diseases.

Approximately 90% of patients with the hematological malignancies termed the chronic myeloproliferative neoplasms harbor either the JAK2V617F-mutation or CALR exon 9 mutation. Both of these are recognized by T-cells, which make the mutations ideal targets for cancer immune therapy as they are shared antigens.

T-cell-mediated immune responses play a fundamental role in controlling Mycobacterium tuberculosis (M. tuberculosis) infection, and traditionally, this response is thought to be mediated by Th1-type CD4+ T-cells secreting IFN-γ. While studying the function and specificity of M. tuberculosis-reactive CD4+ T-cells in more detail at the single cell level; however, we found a human CD4+ T-cell population with a naive phenotype that interestingly was capable of producing multiple cytokines (TCNP cells). CD4+ TCNP cells phenotyped as CD95lo CD28int CD49dhi CXCR3hi and showed a broad distribution of T cell receptor Vβ segments. They rapidly secreted multiple cytokines in response to different M. tuberculosis antigens, their frequency was increased during active disease, but was comparable to latent tuberculosis infection in treated TB patients. These results identify a novel human CD4+ T-cell subset involved in the human immune response to mycobacteria, which is present in active TB patients' blood. These results significantly expand our understanding of the immune response in infectious diseases. [ABSTRACT FROM AUTHOR]

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 103 CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens through the destruction of crucial cells in the immune system, such as the helper T cells, dendritic cells, and macrophages. Since the first case was isolated in the 20th century, the disease has spread rapidly among humans, with significant renal, cardiovascular, respiratory, and neurological complications. It is predominantly sexually transmitted but non-sexual transmission. A relationship between HIV and renal diseases has been suggested for a long time, but only a few systematic studies have centered on this association. This systematic review aims to analyze the possible association between HIV and renal diseases as well as the range and pathogenesis of these renal diseases. HIV remains a critical infectious disease globally, inciting substantial morbidity and mortality. Studies have shown that people living with HIV (PLWH) are at increased risk of acute and chronic kidney disease. This review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and Cochrane databases were searched exhaustively using the inclusion criteria of free full-text English papers that have exclusively studied humans in the last 20 years. Sixteen articles were selected including a systematic review, observational studies, and comprehensive narrative reviews on the role of HIV in the etiology of renal diseases, and were systemically reviewed and analyzed to elicit the wide range of possible renal complications resulting from HIV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yussuf et al.)

In this paper, we construct an HIV infection model which includes latent infection, logistic growth for healthy CD4 T-cells, and antiretroviral therapy. We obtain the global asymptotic stability of the uninfected equilibrium by constructing a Lyapunov function, and we give a sufficient condition for the local asymptotic stability of the infected equilibrium. We also use the latin hypercube sampling technique to identify the key parameters in determining the stability of the infected equilibrium. By numerical simulations, we observe that the model without logistic growth would underestimate the number of infectious virions, while the model without latent infection would overestimate the number of infectious virions. [ABSTRACT FROM AUTHOR]

HIV-1 is an RNA enveloped virus that preferentiallyinfects CD4+ T lymphocytes andalso macrophages. In CD4+ T cells, HIV-1mainly buds from the host cell plasma membrane.The viral Gag polyprotein targets theplasma membrane and is the orchestrator ofthe HIV assembly as its expression is sufficientto promote the formation of virus-likeparticles particles carrying a lipidic envelopederiving from the host cell membrane. Certainlipids are enriched in the viral membraneand are thought to play a key role in theassembly process and the envelop composition.A large body of work performed oninfected CD4+ T cells has provided importantknowledge about the assembly process andthe membrane virus lipid composition. WhileHIV assembly and budding in macrophages isthought to follow the same general Gag-drivenmechanism as in T-lymphocytes, the HIV cyclein macrophage exhibits specific features.In these cells, new virions bud from the limitingmembrane of seemingly intracellular compartments,where they accumulate while remaininginfectious. These structures are now oftenreferred to as Virus Containing Compartments(VCCs). Recent studies suggest that VCCsrepresent intracellularly sequestered regionsof the plasma membrane, but their precisenature remains elusive. The proteomic andlipidomic characterization of virions producedby T cells or macrophages has highlightedthe similarity between their composition andthat of the plasma membrane of producercells, as well as their enrichment in acidiclipids, some components of raft lipids andin tetraspanin-enriched microdomains. Greatchances are that Gag promotes the coalescenceof these components into an assemblyplatform from which viral budding takesplace. How Gag exactly interacts with membranelipids and what are the mechanisms involvedin the interaction between the differentmembrane nanodomains within the assemblyplatform remains unclear. Here we review recentliterature regarding the role of Gag andlipids

Background: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are global health concerns. Due to shared routes of transmission, co-infection is common. Their co-existence can cause severe liver complications and immunological impairment in infected individuals. Aim: To find the prevalence of HBV co-infection in HIV patients and to assess the pattern of liver enzymes and CD4 T -cell counts in HIV monoinfected and HIV/HBV co-infected patients. Materials and Methods: A total of 342 consecutive confirmed HIV positive treatment naïve patients were tested for hepatitis B surface antigen (HBsAg). Clinical staging was done according to Centers for Disease Control and Prevention classification guidelines. Liver function tests were performed by an autoanalyser. CD4 T-cells were estimated by FACS Calibur. Results: Hepatitis B virus co-infection was detected in 8.7% of HIV positive patients as compared to 1.42% in the HIV negative control group (P < 0.05). Majority of the HIV monoinfected and co-infected patients were below 38 years. HBsAg positivity was higher in males (9.4%) and the route of transmission was heterosexual. Categorical data revealed significantly higher proportion of alanine aminotransferase and aspartate aminotransferase (AST) in the co-infected patients compared to the monoinfected patients (P < 0.05). The HIV/HBV co-infected patients had significantly lower CD4 T-cell counts (P = 0.03) and significantly higher AST, alkaline phosphatase and serum bilirubin values (P = 0.023, P = 0.029, P = 0.009 respectively) than the monoinfected group. Males had 1.33 times higher risk than females for co-infection (odds ratio = 1.33; 95% confidence interval 0.57-3.10). Conclusion: The prevalence of co-infection was high. Raised levels of liver enzymes and lowered CD4 counts were seen in co-infected patients. These findings underscore the importance of HBV screening of all HIV positive individuals before initiating antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and <500/mL were selected to receive RLT for 3 months from M0 to M3. Patients had 7 sequential viro-immunological determinations from M-1 to M5. Immune phenotypes were determined by flow cytometry and TID quantification was performed using PCR assay on purified cells. TID (median values) at the initiation of RLT in CD4 T-cells was 117 copies/millions of cells, decreased to 27.5 on M3, and remained thereafter permanently under the cut-off (<10 copies/millions of cells) in 4 out of 6 patients. This was associated with an increase of CD4 and CD4 + CD28+ T-cells and a decrease of HLA-DR expression and apoptosis of CD4 T-cells. RLT inclusion led to decreases in the viral load along with positive immune reconstitution, mainly for CD4 T-cells in HIV patients. [ABSTRACT FROM AUTHOR]

Background: The recent development of eosinophil-targeting agents has raised enthusiasm for management of patients with hypereosinophilic syndromes. Roughly half of anti-IL-5-treated patients with corticosteroid-responsive lymphocytic (L-HES) and idiopathic disease variants can be tapered off corticosteroids. Potential consequences of corticosteroid-withdrawal on clonal expansion of pre-malignant CD3-CD4+ T-cells associated with L-HES are a subject of concern. Indeed, corticosteroid treatment inhibits T-cell activation and may lower blood CD3-CD4+ cell counts. On the other hand, previous studies have shown that eosinophils support CD4 T-cell activation, suggesting that targeted eosinophil depletion may negatively regulate these cells. Objectives: Effects of eosinophils on CD4 T-cell activation in vitro were investigated as an indirect means of exploring whether treatment-induced eosinophil depletion may affect pathogenic T-cells driving L-HES. Methods: Helper (CD4) T-cells and CD3-CD4+ cells from healthy controls and L-HES patients, respectively, were cultured in vitro in presence of anti-CD3/CD28 or dendritic cells. Effects of eosinophils on T-cell proliferation and cytokine production were investigated. Results: Eosinophils enhanced CD3-driven proliferation of CD4 T-cells from healthy subjects in vitro, while inhibiting TCR-independent proliferation and IL-5 production by CD3-CD4+ T-cells. Conclusions: While this study confirms previous work showing that eosinophils support activation of normal helper T-cells, our in vitro findings with CD3-CD4+ T-cells suggest that eosinophil-depletion may favor activation and expansion of this pathogenic lymphocyte subset. With the ongoing development of eosinophil-targeted therapy for various eosinophilic conditions, the indirect consequences of treatment on the underlying immune mechanisms of disease should be investigated in detail in the setting of translational research programs. [ABSTRACT FROM AUTHOR]

Abstract: Cytokine secretion by leukocytes is an important indicator of immune response to pathogens and therefore has significant implications in disease diagnostics. Given heterogeneity of leukocyte subsets and the ability of multiple cell subsets to secrete the same cytokines, connecting cytokine production to a specific leukocyte subset is a distinct challenge. In the present paper we describe a strategy combining antibody (Ab)-based affinity cell separation and surface plasmon resonance (SPR) for capturing human CD4 T-cells and for label-free detection of cell-secreted interferon (IFN)-γ – an important inflammatory cytokine. Human blood was introduced into a flow chamber modified with anti-CD4 Abs resulting in capture of CD4+ T-cells. After mitogenic activation of cells inside the flow chamber, culture medium was routed onto an SPR chip modified with monoclonal IFN-γ Abs. SPR signal observed in this experiment correlated with cytokine production by T-cells. The strategy of combining SPR detection with cell purification may be used in the future for label-free, sensitive detection of multiple cytokines or proteins secreted by the desired cell subset. [Copyright &y& Elsevier]

A ranking of gluten T-cell epitopes triggering celiac disease (CD) for its potential application in the safety assessment of innovative food proteins is developed. This ranking takes into account clinical relevance and information derived from key steps involved in the CD pathogenic pathway: enzymatic digestion, epitope binding to HLA-DQ receptors of the antigen-presenting cells and activation of pro-inflammatory CD4 T-cells, which recognizes the HLA-DQ-epitope complex and initiates the inflammatory response. In silico chymotrypsin digestion was the most discriminatory tool for the ranking of gluten T-cell epitopes among all digestive enzymes studied, classifying 81% and 60% of epitopes binding HLA-DQ2.5 and HLA-DQ8 molecules, respectively, with a high risk. A positive relationship between the number of prolines and the risk of gluten T-cell epitopes was identified. HLA-binding data analysis revealed the additional role played by the flanking regions of the 9-mer epitopes whereas the integration of T-cell activation data into the ranking strategy was incomplete because it was difficult to combine results from different studies. The overall ranking proposed in decreasing order of immunological relevance was: α-gliadins > ω-gliadins > hordeins > γ-gliadins ∼ avenins ∼ secalins > glutenins. This novel approach can be considered as a first step to reshape the risk assessment strategy of innovative proteins and their potential to trigger CD. • There is a need for a new strategy for the assessment of innovative/novel proteins. • A safety ranking of gluten T-cell epitopes triggering celiac disease was developed. • In silico chymotrypsin digestion is one of the most discriminatory tools for ranking. • The number and position of prolines in the epitopes assessed play a significant role. • Ranking by immunological relevance: α-glia > ω-glia > hor > γ-glia ∼ ave ∼ sec > glut. [ABSTRACT FROM AUTHOR]

Data from human studies and animal experiments indicate a dominant role of T-cells over antibodies in controlling acute Lassa virus infection and providing immunity to reinfection. Knowledge of the epitopes recognized by T-cells may therefore be crucial to the development of a recombinant Lassa virus vaccine. In order to study human T-cell reactivity to the most conserved structural protein of Lassa virus, the glycoprotein 2 (GP2), seven GP2-specific CD4+ T-cell clones (TCCs) were generated from the lymphocytes of a Lassa antibody positive individual. All TCC displayed high specific proliferation, showed DR-restriction, and produced IFN-γ upon stimulation with recombinant GP2. The epitope of four of the clones was localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (aa 289–301, numbering according to sequence of GPC). This epitope is conserved in all strains of Lassa virus and lymphocytic choriomeningitis virus (LCMV), shows >90% similarity in all New World arenaviruses of clade B, and overlaps with the proposed fusion domain of GP2. Peptides with conservative aa exchanges, as they naturally occur in the epitope 289–301 of the Old World arenavirus Mopeia and some New World arenaviruses, continued to effectively stimulate the Lassa-GP2-specific T-cell clones tested. The finding of a human T-helper cell epitope, which is highly conserved between Old and New World arenaviruses, is of importance for the design of arenavirus vaccines. [Copyright &y& Elsevier]

Objective: Sudden cardiac death (SCD) plays an important part in all-cause mortality in patients infected with human immunodeficiency virus (HIV). The T-peak to T-end (Tp-e) interval, corrected Tp-e (Tp-ec) interval, and Tp-e/QT ratio on the ECG are parameters used to stratify risk for SCD. The objective of this study was to investigate the differences between HIV-infected patients and healthy individuals in terms of Tp-e interval, Tp-ec interval, and Tp-e/QT ratio, as well as other influencing factors., Methods: Ninety-eight HIV-infected patients and 62 healthy controls were included in this prospective case-control study. Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were measured in all participants. Echocardiographic examination and routine laboratory analysis were performed. In addition, CD4 T-cell count and HIV RNA levels were assessed in HIV-infected patients., Results: All baseline characteristics were comparable in both groups. The median survival of those living with HIV was 20.63 months; 53% of them had controlled viral load, and 74% were receiving antiretroviral therapy. Mean baseline CD4 T-cell count was 409. In HIV-infected patients, the Tp-e interval and Tp-ec interval were prolonged, and the Tp-e/QT ratio was higher (p<0.001, p<0.001 and p=0.021, respectively). In bivariate and partial correlation analyses, there was a negative correlation between CD4 T-cell level and Tp-e interval, Tp-ec interval, and Tp-e/QT ratio., Conclusion: Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were greater in HIV-infected patients compared with healthy individuals. HIV-infected patients, particularly those with low baseline CD4 T-cell counts, should be closely monitored due to risk of SCD., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)