scholarly journals RNA sequencing of CD4 T-cells reveals the relationships between lncRNA-mRNA co-expression in elite controller vs. HIV-positive infected patients

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8911
Author(s):  
Chaoyu Chen ◽  
Xiangyun Lu ◽  
Nanping Wu
Keyword(s):  
T Cells ◽  
Rna Sequencing ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
Pearson Correlation ◽  
Elite Controller ◽  
Hiv Positive ◽  
Elite Controllers ◽  
Functional Relationships

Background Elite controller refers to a patient with human immunodeficiency virus infection with an undetected viral load in the absence of highly active antiretroviral therapy. Studies on gene expression and regulation in these individuals are limited but significant, and have helped researchers and clinicians to understand the interrelationships between HIV and its host. Methods We collected CD4 T-cell samples from two elite controllers (ECs), two HIV-positive infected patients (HPs), and two healthy controls (HCs) to perform second-generation transcriptome sequencing. Using the Cufflinks software, we calculated the Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) and identified differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs), with corrected P value < 0.05 (based on a false discovery rate (FDR) < 0.05). We then constructed a protein-protein interaction network using cytoHubba and a long non-coding RNA-mRNA co-expression network based on the Pearson correlation coefficient. Results In total, 1109 linear correlations of DE lncRNAs targeting DE mRNAs were found and several interesting interactions were identified as being associated with viral infections and immune responses within the networks based on these correlations. Among these lncRNA-mRNA relationships, hub mRNAs including HDAC6, MAPK8, MAPK9, ATM and their corresponding annotated co-expressed lncRNAs presented strong correlations with the MAPK-NF-kappa B pathway, which plays a role in the reactivation and replication of the virus. Conclusions Using RNA-sequencing, we systematically analyzed the expression profiles of lncRNAs and mRNAs from CD4+ T cells from ECs, HPs, and HCs, and constructed a co-expression network based on the relationships among DE transcripts and database annotations. This was the first study to examine gene transcription in elite controllers and to study their functional relationships. Our results provide a reference for subsequent functional verification at the molecular or cellular level.

scholarly journals CD4 T-cell transcriptome expression reversal of the lncRNA-mRNA co-expression network in elite controllervs.normal-process HIV patients

2019 ◽  
Author(s):  
Chaoyu Chen ◽  
Xiangyun Lu ◽  
Nanping Wu
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Pearson Correlation ◽  
Differentially Expressed ◽  
Cd4 T Cell ◽  
Elite Controller ◽  
Normal Process ◽  
Elite Controllers ◽  
Functional Relationships ◽  
Non Coding Rnas

AbstractElite controller refers to a patient with human imunodeficienvcy virus infection with an undetected viral load without anti-viral treatment. Studies on gene expression and regulation in these individuals are limited but significant. We enrolled 196 patients and collected CD4 T-cell samples from two elite controllers, two normal-process infected patients, and two healthy controls to perform second-generation transcriptome sequencing. Using the Cuffdiff model, we identified differentially expressed mRNAs and long non-coding RNAs with corrected P value < 0.05, and constructed a protein-protein interaction network as well a long non-coding RNA-mRNA co-expression network based on the Pearson correlation coefficient. Interestingly, some interactions within the networks were identified as associated with viral infections and immune responses. This was the first study to examine gene transcription in elite controllers and to study their functional relationships. Our results provide a reference for subsequent functional verification at the molecular or cellular level.Author SummarySome individuals can spontaneously inhibit HIV replication after infection with HIV, and thus lack any symptoms. Studies on these patients, termed elite controllers (ECs) will help researchers and clinicians to understand the interrelationship between HIV and the host. In the present study, we focused on the interactions and functional relationships between significantly differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in ECsvs. normal-process patients (NPs). RNA-sequencing was performed for six representative samples of CD4 T-cells. Using the Pearson correlation test, an lncRNA-mRNA co-expression network was constructed. Several new regulatory relationships between transcripts were revealed that might be closely related to the ability of ECs to maintain a low viral load for long periods without anti-viral treatment. For example, lncRNAC3orf35was upregulated in ECsvs. NPs and was positively related to downregulation ofGNG2mRNA (encoding G protein subunit gamma 2), which functions in chemokine signaling pathways and HIV-1 infection. Overall, we identified certain interesting genetic interactions that will provide information about the mechanism of host suppression of viral replication.

scholarly journals Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells

2008 ◽  
Vol 81 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Gautam K. Sahu ◽  
David Paar ◽  
Simon D.W. Frost ◽  
Melissa M. Smith ◽  
Scott Weaver ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Low Level ◽  
Highly Active

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 Tenofovir-Based Highly Active Antiretroviral Therapy Is Associated with Superior CD4 T Cells Repopulation Compared to Zidovudine-Based HAART in HIV 1 Infected Adults

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Vitus Sambo Badii ◽  
Kwame Ohene Buabeng ◽  
Thomas Agyarko Poku ◽  
Arnold Donkor Forkuo ◽  
Bright Boafo Boamah ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Scientific Data ◽  
Highly Active ◽  
Median Period ◽  
Hiv 1 ◽  
Count Change ◽  
Zidovudine Regimen

Tenofovir-based highly active antiretroviral therapy (HAART) is one of the preferred first-line therapies in the management of HIV 1 infection. Ghana has since 2014 adopted this recommendation; however there is paucity of scientific data that reflects the safety and efficacy of the tenofovir-based therapy compared to zidovudine in the Ghanaian health system. This study sought to assess the comparative immune reconstitution potential between tenofovir and zidovudine-based HAART regimens, which includes lamivudine and efavirenz in combination therapy. It also aimed to investigate the adverse drug reactions/events (ADREs) associated with pharmacotherapy with these agents in a total of 106 HAART naïve HIV patients. The study included 80 patients in the tenofovir cohort while 26 patients were on the zidovudine regimen. The occurrence of HIV comorbidities profile was assessed at diagnosis and throughout the study period. The baseline CD4 T cells count of the participants was also assessed at diagnosis and repeated at a median period of five months (range 4–6 months), after commencing treatment with either tenofovir- or zidovudine-based HAART. After five months of the HAART, the tenofovir cohort recorded higher CD4 T cell count change from baseline compared to the zidovudine cohort (p<0.0001). The patients on the tenofovir-based HAART and female sex however appeared to be associated with more multiple ADREs.

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