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

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.

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8911
Author(s):  
Chaoyu Chen ◽  
Xiangyun Lu ◽  
Nanping Wu

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.


2009 ◽  
Vol 50 (1) ◽  
pp. 65-76 ◽  
Author(s):  
Vladimir Novitsky ◽  
Elias Woldegabriel ◽  
Lemme Kebaabetswe ◽  
Raabya Rossenkhan ◽  
Busisiwe Mlotshwa ◽  
...  
Keyword(s):  
T Cell ◽  

2017 ◽  
Vol 9 (1) ◽  
pp. 2017049 ◽  
Author(s):  
Lassina TRAORE ◽  
Ouéogo NIKIEMA ◽  
Abdoul Karim OUATTARA ◽  
Tegwindé Rébéca COMPAORE ◽  
Serge Théophile SOUBEIGA ◽  
...  

Epstein Barr Virus (EBV) and Human Herpes Virus 6 (HHV-6) are responsible for severe diseases, particularly in immunocompromised persons. There are poor data on the infection with these opportunistic viruses in Burkina Faso.The purpose of this study is to characterize EBV and HHV-6 subtypes and to assess their impact on CD4 T cell count, HIV-1 viral load and antiretroviral treatment in people living with HIV-1.The study population consisted of 238 HIV-positive patients with information on CD4 count, HIV-1 viral load and HAART. Venous blood samples collected on EDTA tubes were used for EBV and HHV-6 Real Time PCR subtyping.An infection rate of 6.7% (16/238) and 7.1% (17/238) were found respectively for EBV and HHV-6 in the present study. Among EBV infections, similar prevalences were noted for both subtypes (3.9% [9/238] for EBV-1 vs 4.6% [11/238] for EBV-2) with 2.1% (5/238) of co-infection. HHV-6A infection represented 6.3% (15/238) of the study population against 5.0% (12/238) for HHV-6B. . EBV-2 infection was significantly higher in patients with CD4 count ≥ 500 compared to those with CD4 count less than 500 cells (1.65% vs 8.56%, p = 0,011). The prevalence of EBV and HHV-6 infections were almost similar in HAART-naive and HAART-experienced patients.The present study provides information on the prevalence of EBV and HHV-6 subtypes in people living with HIV-1 in Burkina Faso. The study also suggests that HAART treatment has no effect on infection with these opportunistic viruses in people living with HIV-1.


2018 ◽  
Vol 67 (5) ◽  
pp. 821-825
Author(s):  
Suleyman Sezai Yildiz ◽  
Sukru Cetin ◽  
Kudret Keskin ◽  
Alper Gunduz ◽  
Gokhan Cetinkal ◽  
...  

The pathophysiology of an early and accelerated atherosclerotic process is complex and multifactorial in HIV-infected men compared with HIV-non-infected men. Several biomarkers have been well studied in the detection of the early stage of atherosclerosis, but studies are limited in HIV-infected men. The objective of this study was to investigate the association between serum pregnancy-associated plasma protein-A (PAPP-A) and carotid intima-media wall thickness (CIMT) in asymptomatic HIV-infected men. This a case–control study group comprising 118 HIV-infected men and 60 age-matched and gender-matched HIV-non-infected men. Serum PAPP-A was measured using an ELISA kit and carotid IMT was evaluated by Doppler ultrasonography in all subjects. Statistical analysis included receiver-operating characteristic (ROC) analysis, Pearson correlation and logistic regression analysis. Serum PAPP-A level was significantly higher in HIV +CIMT+ group compared with HIV +CIMT group and HIV–CIMT- group. We found a positive correlation between PAPP-A and increased CIMT (r=0.737, p<0.0001), and a negative correlation between nadir CD4 T cell counts and increased CIMT (r=−0.526, p<0.001). In multivariate logistic regression analyses, PAPP-A, nadir CD4 T cell count and age were significantly associated with subclinical atherosclerosis (p<0.001, p=0.006 and p=0.032, respectively). In ROC analysis, PAPP-A levels of >3.70 µg/mL were associated with subclinical atherosclerosis in HIV+ men with a specificity of 100% and a sensitivity of 71% (area under the curve: 0.949, 95% CI 0.875 to 1.000, p<0.001). Serum PAPP-A level was strongly correlated with increased CIMT in HIV-infected men. PAPP-A might be used as an early biomarker to identify atherosclerosis in asymptomatic HIV-infected men.


Retrovirology ◽  
2014 ◽  
Vol 11 (S1) ◽  
Author(s):  
Mariana T Pinto ◽  
Tathiane M Malta ◽  
Daniel G Pinheiro ◽  
Evandra S Rodrigues ◽  
Rodrigo A Panepucci ◽  
...  

2011 ◽  
Vol 86 (1) ◽  
pp. 277-283 ◽  
Author(s):  
S. Ranasinghe ◽  
M. Flanders ◽  
S. Cutler ◽  
D. Z. Soghoian ◽  
M. Ghebremichael ◽  
...  

Author(s):  
Stephane Isnard ◽  
Rayoun Ramendra ◽  
John Lin ◽  
Sanket Kant ◽  
Brandon Fombuena ◽  
...  

Abstract Elite controllers (ECs) are people living with human immunodeficiency virus (HIV) who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-cytomegalovirus (CMV) immunoglobulin G (IgG) levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex, and human leukocyte antigen (HLA) type. Elevated anti-CMV titers may favor disease progression in ECs.


PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0224723 ◽  
Author(s):  
Joseph B. Sempa ◽  
Theresa M. Rossouw ◽  
Emmanuel Lesaffre ◽  
Martin Nieuwoudt

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