scholarly journals Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Expression Profiles ◽  
Critical Role ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Target Mrnas ◽  
Immunodeficiency Virus ◽  
Mirna Sequencing ◽  
Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

scholarly journals HIV-1 Infection Transcriptomics: Meta-Analysis of CD4+ T Cells Gene Expression Profiles

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 244 ◽  
Author(s):  
Antonio Victor Campos Coelho ◽  
Rossella Gratton ◽  
João Paulo Britto de Melo ◽  
José Leandro Andrade-Santos ◽  
Rafael Lima Guimarães ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Differentially Expressed Genes ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Infected Cells ◽  
Hiv 1

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting. This study aims at performing a meta-analysis of RNA-Seq expression profiles in samples of HIV-1 infected CD4+ T cells compared to uninfected cells to assess consistently differentially expressed genes in the context of HIV-1 infection. We selected two studies (22 samples: 15 experimentally infected and 7 mock-infected). We found 208 differentially expressed genes in infected cells when compared to uninfected/mock-infected cells. This result had moderate overlap when compared to previous studies of HIV-1 infection transcriptomics, but we identified 64 genes already known to interact with HIV-1 according to the HIV-1 Human Interaction Database. A gene ontology (GO) analysis revealed enrichment of several pathways involved in immune response, cell adhesion, cell migration, inflammation, apoptosis, Wnt, Notch and ERK/MAPK signaling.

scholarly journals Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death

2005 ◽  
Vol 79 (5) ◽  
pp. 3195-3199 ◽  
Author(s):  
Jean-Daniel Lelièvre ◽  
Frédéric Petit ◽  
Damien Arnoult ◽  
Jean-Claude Ameisen ◽  
Jérôme Estaquier
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Infection ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1LAI) primes CD8+ T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8+ T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8+ T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4+ and CD8+ T-cell death induced by HIV-1LAI. Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1LAI and IL-7 is one of the mechanisms involved in progression to AIDS.

scholarly journals Myeloid-derived suppressor cells and the pathogenesis of human immunodeficiency virus infection

Open Biology ◽  
2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Mahmoud Mohammad Yaseen ◽  
Nizar Mohammad Abuharfeil ◽  
Homa Darmani
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Hiv Infection ◽  
Immune Activation ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Chronic Immune Activation ◽  
Immune Suppressor Cells ◽  
Immunodeficiency Virus ◽  
Immune Suppressor

There are several mechanisms by which human immunodeficiency virus (HIV) can mediate immune dysfunction and exhaustion during the course of infection. Chronic immune activation, after HIV infection, seems to be a key driving force of such unwanted consequences, which in turn worsens the pathological status. In such cases, the immune system is programmed to initiate responses that counteract unwanted immune activation, for example through the expansion of myeloid-derived suppressor cells (MDSCs). Although the expansion of immune suppressor cells in the setting of systemic chronic immune activation, in theory, is expected to contain immune activation, HIV infection is still associated with a remarkably high level of biomarkers of immune activation. Paradoxically, the expansion of immune suppressor cells during HIV infection can suppress potent anti-viral immune responses, which in turn contribute to viral persistence and disease progression. This indicates that HIV hijacks not only immune activation but also the immune regulatory responses to its advantage. In this work, we aim to pave the way to comprehend how such unwanted expansion of MDSCs could participate in the pathology of acute/primary and chronic HIV infection in humans, as well as simian immunodeficiency virus infection in rhesus macaques, according to the available literature.

Integrated analysis profiles of long non–coding RNAs reveal potential biomarkers across brain regions in post–traumatic stress disorder

2020 ◽  
Author(s):  
Yaoyao Bian ◽  
Lili Yang ◽  
Zhongli Wang ◽  
Wen Li ◽  
Qing Wang ◽  
...  
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Post Traumatic Stress ◽  
Post Traumatic ◽  
Non Coding Rnas ◽  
Potential Biomarkers

Abstract Background Post–traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety and depression. However, underlying mechanisms, especially the function roles of long non–coding RNAs (lncRNAs) involved in PTSD is still unclear. We argued that the lncRNAs, co–expressed mRNAs, as well as the associated pathways, are altered and may thus serve as potential biomarkers and key pathways related to PTSD.Methods The gene expression profiles of GSE68077 was downloaded from the GEO database, and the differentially expressed lncRNAs and mRNAs were identified. Gene ontology (GO) and Kyto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis were performed. Subsequently, protein–protein interaction (PPI) network was analyzed, and module analysis of the differentially expressed mRNAs was performed with Cytoscape software. Finally, lncRNAs–mRNAs co–expression network was constructed and core pair lncRNAs involved in PTSD were mapped.Results A total of 45 differentially expressed lncRNAs and 726 differentially expressed mRNAs were obtained. Among of which, 17 lncRNAs and 86 mRNAs were inter–regulated, and most of the lncRNAs–mRNAs co–expression showed positive correlations. The lncRNAs–mRNAs co–expressed network suggested the potentially functional roles of lncRNAs, regulated mRNAs and related pathways in PTSD. By implication of the core pair network, lncRNA–NONMMUT010120.2 synergistically up–regulated Ppargc1a and down–regulated Cir1, Slc38a9, Atp6v0a2. Moreover, lncRNA–NONMMUT023440.2, NONMMUT034155.2, NONMMUT105407.1 and NONMMUT149972.1 were co–expressed with 10 co–expressed mRNAs, which indicated that lncRNAs involved in PTSD might work by regulating the co–expressed mRNAs.

scholarly journals Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 76 ◽  
Author(s):  
Mitch Brinkkemper ◽  
Kwinten Sliepen
Keyword(s):  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibodies ◽  
Viral Membrane ◽  
Immunodeficiency Virus ◽  
Hiv 1

The enormous sequence diversity between human immunodeficiency virus type 1 (HIV-1) strains poses a major roadblock for generating a broadly protective vaccine. Many experimental HIV-1 vaccine efforts are therefore aimed at eliciting broadly neutralizing antibodies (bNAbs) that are capable of neutralizing the majority of circulating HIV-1 strains. The envelope glycoprotein (Env) trimer on the viral membrane is the sole target of bNAbs and the key component of vaccination approaches aimed at eliciting bNAbs. Multimeric presentation of Env on nanoparticles often plays a critical role in these strategies. Here, we will discuss the different aspects of nanoparticles in Env vaccination, including recent insights in immunological processes underlying their perceived advantages, the different nanoparticle platforms and the various immunogenicity studies that employed nanoparticles to improve (neutralizing) antibody responses against Env.

Late diagnosis of human immunodeficiency virus infections in high-risk groups in Karachi, Pakistan

2018 ◽  
Vol 29 (14) ◽  
pp. 1400-1406
Author(s):  
Zahra Hasan ◽  
Sharaf Shah ◽  
Rumina Hasan ◽  
Shoaib Rao ◽  
Manzoor Ahmed ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Early Diagnosis ◽  
Hiv Infection ◽  
Hiv Infections ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human immunodeficiency virus (HIV) infection prevalence in Pakistan has been increasing in high-risk groups, including people who inject drugs (PWID) and transgender hijra sex workers (TG-HSWs) nationwide. Effective control of HIV requires early diagnosis of the infection. We investigated recency of HIV infections in newly-diagnosed cases in PWID and TG-HSWs. This was an observational study with convenience sampling. Overall, 210 HIV-positive subjects comprising an equal number of PWID and TG-HSWs were included. Antibody avidity was tested using the Maxim HIV-1 Limiting Antigen Avidity (LAg) EIA (Maxim Biomedical, Inc. Rockville, Maryland, USA). The mean age of study subjects was 29.5 years: PWID, 28.5 years and TG-HSWs, 30.4 years. Study subjects were married, 27%, or unmarried. Eighteen percent of individuals had recently-acquired HIV infections: 19% of PWID and 17% of TG-HSWs. Eighty-two percent of individuals had long-term HIV infections: 81% of PWID and 83% of TG-HSWs. This is the first study identification of recent HIV-1 infections in Pakistan. We show that most newly-diagnosed HIV patients in the high-risk groups studied had long-term infections. There is an urgent need for intervention in these groups to facilitate early diagnosis and treatment of HIV infection to reduce transmission in Pakistan.

Genetically identical primate modelling systems for HIV vaccines

1998 ◽  
Vol 10 (8) ◽  
pp. 651 ◽  
Author(s):  
Stephen J. Kent ◽  
Ian M. Lewis
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
Vaccine Development ◽  
Careful Consideration ◽  
Hiv Vaccine ◽  
Effective Vaccine ◽  
Hiv Vaccines ◽  
Major Step ◽  
Immunodeficiency Virus ◽  
Hiv 1

There is an urgent need for a safe and effective vaccine to prevent human immunodeficiency virus (HIV) infection. Several HIV vaccine candidates have shown promise, but many concerns regarding the safety and efficacy of current vaccines remain. A major hindrance in HIV vaccine development is a poor understanding of precisely what functions HIV vaccines are required to perform in order to protect humans from HIV-1. Only higher primates (i.e. macaques, chimpanzees and humans) are susceptible to HIV-1 or the closely related virus ‘simian immunodeficiency virus’. These species are outbred and there are remarkable genetic differences in both the immune responses to vaccines and their susceptibility to infection. The development of genetically identical macaques would be a major step towards dissecting what immune responses are required to protect from HIV infection. For example, live attenuated HIV-1 vaccines are likely to be highly efficacious, but will induce disease in a substantial proportion of recipients. Defining why a live attenuated vaccine is effective should allow safer vaccines to be developed, retaining only the immunologic properties of an effective vaccine. The reduction in ‘background genetic noise’ obtained by studying genetically identical primates would provide concise answers to critical HIV vaccine issues, by studying a minimal number of animals. Such an approach could potentially be employed in other diseases where non-human primates are the only available model. Small studies can be performed where identical twins are generated by embryo bisection; however, larger studies where multiple immune parameters are simultaneously evaluated would be facilitated by cloning technology. Despite the technical difficulties to be overcome, the potential gains in human health from the development of genetically identical non-human primates are worthy of careful consideration.

scholarly journals 1265. Monitoring of Human Immunodeficiency Virus (HIV)-Infection Using the Cepheid HIV-1 Qualitative Assay

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S455-S455
Author(s):  
Erin Keizur ◽  
Drew Wood-Palmer ◽  
Maryann Koussa ◽  
Manuel Ocasio ◽  
Mary Jane Rotheram-Borus ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Los Angeles ◽  
Hiv Infection ◽  
Whole Blood ◽  
Viral Rna ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Pcr Test

Abstract Background Human immunodeficiency virus (HIV)-1 RNA quantification is the primary method of monitoring response to antiretroviral therapy. In the U.S. viral RNA testing is recommended for all HIV-infected patients at entry into care, at initiation or modification of therapy, and on a regular basis thereafter. HIV-1 DNA testing may pose additional advantages. For example, proviral DNA may predict early loss of viral suppression. The Cepheid® (Sunnyvale, CA) HIV-1 Qualitative (HIV Qual) assay detects total nucleic acid for both RNA and DNA and provides a qualitative result (HIV detectable or undetectable). Methods We tested participants aged 14–24 years old from the Adolescent Trials Network (ATN) CARES study with known HIV infection in Los Angeles, California and New Orleans, Louisiana. We tested participants using the Cepheid® HIV Qual assay and the quantitative HIV-1 RNA, real-time PCR test using the COBAS P6800 system (Roche, Branchburg, NJ). We used 100 μL of whole blood for the HIV Qual assay and results were provided in 90 minutes. We sent the remainder of the whole blood from the same visit to a commercial laboratory for HIV-RNA PCR testing and results were reported as “detected,” “detected, <20 copies/mL plasma” or “not detected, <20 copies/mL plasma.” We compared HIV Qual and HIV RNA PCR test results from the same visit for each participant. Results Overall, 57 HIV Qual tests were performed with concurrent HIV RNA PCR tests. Of those, 9/15 tests were concordant with HIV viral RNA suppression while 39/42 tests were concordant with HIV viral RNA detection. In 6 cases, the HIV RNA was not detected at <20 copies/mL by the Roche PCR while the HIV Qual assay detected HIV DNA. Of those 6 cases, 3 had subsequent HIV RNA PCR testing. All 3 cases had detectable HIV RNA at their next testing date (214 copies/mL, detected <20 copies/mL, 2130 copies/mL). Conclusion The HIV Qual test is feasible for the monitoring of HIV-infection. Due to its detection of HIV DNA, it may predict future lack of HIV RNA suppression. Disclosures All authors: No reported disclosures.

scholarly journals Integrated analysis of the aging brain transcriptome and proteome in tauopathy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Carl Grant Mangleburg ◽  
Timothy Wu ◽  
Hari K. Yalamanchili ◽  
Caiwei Guo ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Mutant Form ◽  
Brain Gene Expression ◽  
Brain Transcriptome ◽  
Age Dependent

Abstract Background Tau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes. Methods Paired, longitudinal RNA-sequencing and mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutant form causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy. Results TauWT induced 1514 and 213 differentially expressed transcripts and proteins, respectively. TauR406W had a substantially greater impact, causing changes in 5494 transcripts and 697 proteins. There was a ~ 70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes. Conclusions Our results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.

Human Immunodeficiency Virus (HIV)-Resistant CD4+ UT-7 Megakaryocytic Human Cell Line Becomes Highly HIV-1 and HIV-2 Susceptible Upon CXCR4 Transfection: Induction of Cell Differentiation by HIV-1 Infection

Blood ◽  
1997 ◽  
Vol 89 (8) ◽  
pp. 2670-2678 ◽  
Author(s):  
Marta Baiocchi ◽  
Eleonora Olivetta ◽  
Cristiana Chelucci ◽  
Anna Claudia Santarcangelo ◽  
Roberta Bona ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Cell Line ◽  
Viral Entry ◽  
Human Cell Line ◽  
Immunodeficiency Virus ◽  
Hiv Entry ◽  
Stromal Cell Derived Factor ◽  
Hiv 1

Abstract Recent findings have shown that the expression of the seven trans-membrane G-protein–coupled CXCR4 (the receptor for the stromal cell-derived factor [SDF]-1 chemokine) is necessary for the entry of T-lymphotropic human immunodeficiency virus (HIV) strains, acting as a coreceptor of the CD4 molecule. In the human system, the role of CXCR4 in HIV infection has been determined through env-mediated cell fusion assays and confirmed by blocking viral entry in CD4+/CXCR4+ cells by SDF-1 pretreatment. We observed that the human megakaryoblastic CD4+ UT-7 cell line fails to express CXCR4 RNA and is fully resistant to HIV entry. Transfection of an expression vector containing the CXCR4 c-DNA rendered UT-7 cells readily infectable by different T-lymphotropic syncytium-inducing HIV-1 and HIV-2 isolates. Interestingly, HIV-1 infection of CXCR4 expressing UT-7 cells (named UT-7/fus) induces the formation of polynucleated cells through a process highly reminiscent of megakaryocytic differentiation and maturation. On the contrary, no morphologic changes were observed in HIV-2–infected UT-7/fus cells. These findings further strengthen the role of CXCR4 as a molecule necessary for the replication of T-lymphotropic HIV-1 and HIV-2 isolates and provide a useful model to study the functional role of CD4 coreceptors in HIV infection.

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