scholarly journals Analysis of Long Noncoding RNA and mRNA Profiling in Peripheral Blood Mononuclear Cells of Human Immunized With Rabies Virus Vaccine by RNA Sequencing

2020 ◽  
Author(s):  
Pingsen Zhao ◽  
Kaijian Hou ◽  
Peibin Zeng ◽  
Songtao Yang ◽  
Xianzhu Xia

Abstract Background Rabies is still a lethal disease caused by rabies virus (RABV), and it remains a global health threaten. The epigenetic landscape of host in response to immunization with rabies virus vaccine is not yet elucidated. Evidences reveal that long noncoding RNA (lncRNA) play an important role for control of viral infection, but the expression profile of lncRNA in human immunized with rabies virus vaccine remains unclear. Methods lncRNA and mRNA profiles were investigated in four volunteers vaccinated with RABV vaccine by RNA sequencing. Results 33 lnRNAs and 427 mRNAs were differentially expressed in RABV vaccine immunized volunteers. The gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analysis the functional annotation, and the result suggested the lncRNAs involved in signaling pathways related to host immune induced by the RABV vaccine. Conclusions To the best of our knowledge, it is the first time to report the transcriptomic landscape of lncRNAs in human immunized with RABV vaccine. Our study mimics the host response of human to RABV infection and suggests that lncRNAs might be of a potential therapeutic target in anti-rabies virus strategies.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Georgiopoulos ◽  
I Mavroeidis ◽  
K Sopova ◽  
M Sacshe ◽  
A Mareti ◽  
...  

Abstract Background Amyloid-beta (1-40) (Aβ1–40), a proinflammatory and pro-atherosclerotic peptide, is associated with accelerated atherosclerosis and major adverse cardiac events. Abeta1–40 production is mainly dependent on the cleavage of amyloid precursor protein by β-amyloid cleaving enzyme-1 (BACE1), known as beta-secretase. BACE1 antisense (BACE1-AS) is a long noncoding RNA that enhances BACE1 stability. Objectives To evaluate the clinical value of plasma amyloid-beta levels and its upstream regulatory pathway BACE1/BACE1-AS in patients with subclinical and established atherosclerotic cardiovascular disease. Methods Plasma levels of Aβ40 were measured in 642 consecutively recruited patients with and without clinically overt coronary artery disease (CAD). BACE1-AS lncRNA and BACE1 mRNA expression were measured in peripheral blood mononuclear cells derived from 214 study participants. Intima-media thickness and atheromatous plaques by ultrasonography, markers of arterial wave reflections and pulse wave velocity were used as surrogate markers of subclinical CVD. Cardiovascular risk factors (CVRFs), including impaired glomerular filtration rate (<60 ml/min), smoking, hypertension, hyperlipidemia, diabetes, obesity and increased hsCRP (>2 mg/l) were assessed as a measure of CVRF burden. Results Both in non-CAD (n=369) and CAD (n=273) patients, Aβ1–40 was associated with age, aortic and peripheral systolic and pulse pressure, and low GFR (p<0.05 for all). In non-CAD subjects Aβ1–40 also correlated with diabetes and low HDL. Importantly, Aβ1–40 was associated with the presence of any plaque in subjects without CAD (p=0.035) and with increased number of diseased coronary arteries (p=0.022) independently of age, gender and CVRFs. Aβ1–40 plasma levels were increased in the highest tertile of BACE1 and BACE1AS (p<0.05) while their expression levels were highly intercorrelated (r=0.825, P<0.001). BACE1 and BACE1-AS levels progressively increased across the 3 groups of non-CAD (n=145), stable CAD (n=43) and acute myocardial infarction (n=26) patients (p for trend<0.001). Among non-CAD subjects, both BACE1 and BACE1-AS were increased in individuals with >2 CVRFs. Among CAD patients, BACE1-AS was associated with decreased LVEF (<50%) (adjusted OR=1.92 per 1-SD increase, p=0.047) while BACE1 in the highest tertile was associated with 5-fold higher odds for coronary multi-vessel disease (p=0.004) after adjustment for age, gender and CVRFs. Conclusions Circulating Aβ1–40 and increased expression of its upstream regulators BACE1/BACE1-AS are intercorrelated and associated with the presence and severity of subclinical and clinically overt atherosclerosis. These findings suggest that BACE1-AS/BACE1-mediated increased availability of Aβ1–40 may play a pivotal role in its adverse cardiovascular effects.


2020 ◽  
Vol 26 ◽  
Author(s):  
Yujie Shen ◽  
Yexiang Lin ◽  
Kai Liu ◽  
Jinlan Chen ◽  
Juanjuan Zhong ◽  
...  

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1018
Author(s):  
Abby C. Lee ◽  
Grant Castaneda ◽  
Wei Tse Li ◽  
Chengyu Chen ◽  
Neil Shende ◽  
...  

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.


2008 ◽  
Vol 89 (6) ◽  
pp. 1329-1337 ◽  
Author(s):  
Heide Niesalla ◽  
Tom N. McNeilly ◽  
Margaret Ross ◽  
Susan M. Rhind ◽  
Gordon D. Harkiss

Experiments were performed to determine whether visna/maedi virus (VMV), a small ruminant lentivirus (SRLV), could infect sheep via ocular tissues. The EV1 strain of VMV was administered into the conjunctival space of uninfected sheep, and the animals monitored for the presence of provirus DNA and anti-VMV antibodies in blood. The results showed that provirus DNA appeared in peripheral blood mononuclear cells of all animals within a few weeks of receiving either 106 TCID50 or 103 TCID50 of VMV. Of the animals receiving the higher dose of virus via the conjunctival space, two seroconverted by 7 and 10 weeks post-infection, one seroconverted 8 months post-infection, and one had not seroconverted by 15 months post-infection. With the lower virus dose, the animals infected via the trachea seroconverted by 4 and 14 weeks, respectively. After ocular infection with this dose, one animal showed a transitory seroconversion with low levels of antibody, peaking at 2 weeks post-administration. The remaining three of the animals infected via the eyes did not seroconvert over a period of 13 months. At post-mortem, evidence for the presence of proviral DNA was obtained from ocular tissue, lungs or mediastinal lymph node in both groups of animals. Histological analysis of lung tissue from animals receiving the lower dose of virus showed the presence of early inflammatory lesions. The results thus show for the first time that transmission of VMV can occur via ocular tissues, suggesting that the conjunctival space may be an additional route of natural transmission.


2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel J. B. Clarke ◽  
Alison W. Rebman ◽  
Allison Bailey ◽  
Megan L. Wojciechowicz ◽  
Sherry L. Jenkins ◽  
...  

Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as from COVID-19 patients, but classification was not successful in distinguishing those patients with early Lyme disease cases that would advance to develop post-treatment persistent symptoms.


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