scholarly journals Hepatitis E rORF2p Stimulated and Unstimulated Peripheral Expression Profiling in Patients with Self-Limiting Hepatitis E Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sanjay B. Rathod ◽  
Anuradha S. Tripathy

To improve the current knowledge on the involvement of peripheral lymphocytes in hepatitis E virus (HEV) associated pathogenesis, we analyzed alterations in (1) immunophenotypic expressions (by flow cytometry) and (2) gene expression patterns (by TaqMan Low Density Array) of activatory, inhibitory, integrin, homing, ectonucleotidase machinery, costimulatory, inflammatory markers, and T regulatory cells (Treg) associated cytokines on HEV rORF2p stimulated and unstimulated PBMCs of 43 acute HEV patients, 30 recovered individuals, and 43 controls. The phenotypic expressions of key molecules CTLA-4, GITR, CD103, CD25, CD69, IL10 and TGF-β1in the acute patients and TGF-β1in the recovered individuals were significantly elevated on both unstimulated and stimulated PBMCs. Gene expression array data revealed upregulations of CD25, PD1, CD103, CCR4, IL10, and TGF-β1on both unstimulated and HEV rORF2p stimulated PBMCs of acute patients. The observed upregulations of inhibitory, integrin, activatory, and Treg-associated cytokine genes on the PBMCs of acute HEV patients complemented by their frequency data suggest them as the major players in the fine-tuning of immune response in self-limiting hepatitis E infection.

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 699
Author(s):  
Anna Mrzljak ◽  
Lorena Jemersic ◽  
Vladimir Savic ◽  
Ivan Balen ◽  
Maja Ilic ◽  
...  

Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally. The first human case of autochthonous HEV infection in Croatia was reported in 2012, with the undefined zoonotic transmission of HEV genotype 3. This narrative review comprehensively addresses the current knowledge on the HEV epidemiology in humans and animals in Croatia. Published studies showed the presence of HEV antibodies in different population groups, such as chronic patients, healthcare professionals, voluntary blood donors and professionally exposed and pregnant women. The highest seroprevalence in humans was found in patients on hemodialysis in a study conducted in 2018 (27.9%). Apart from humans, different studies have confirmed the infection in pigs, wild boars and a mouse, indicating the interspecies transmission of HEV due to direct or indirect contact or as a foodborne infection. Continued periodical surveys in humans and animals are needed to identify the possible changes in the epidemiology of HEV infections.


Lupus ◽  
2017 ◽  
Author(s):  
Konstantinos Tselios ◽  
Alexandros Sarantopoulos ◽  
Ioannis Gkougkourelas ◽  
Panagiota Boura

Author(s):  
Anne M. Pesenacker ◽  
Lucy R. Wedderburn

In recent years, there have been many new developments in the field of regulatory T cells (Treg), challenging the consensus on their behaviour, classification and role(s) in disease. The role Treg might play in autoimmune disease appears to be more complex than previously thought. Here, we discuss the current knowledge of regulatory T cells through animal and human research and illustrate the recent developments in childhood autoimmune arthritis (juvenile idiopathic arthritis (JIA)). Furthermore, this review summarises our understanding of the fields and assesses current and future implications for Treg in the treatment of JIA.


2021 ◽  
Author(s):  
Ricardo N Ramirez ◽  
Kaitavjeet Chowdhary ◽  
Juliette Leon ◽  
Diane Mathis ◽  
Christophe Benoist

Gene expression programs are specified by higher-order chromatin structure and enhancer-promoter loops (EPL). T regulatory cells (Treg) identity is dominantly specified by the transcription factor FoxP3, whose mechanism of action is unclear. We applied proximity-ligation with chromatin immunoprecipitation (HiChIP) in Treg and closely related conventional CD4+ T cells (Tconv). EPL identified by H3K27Ac HiChIP showed a range of connection intensity, with some super-connected genes. TF-specific HiChIP showed that FoxP3 interacts with EPLs at a large number of genes, including some not differentially expressed in Treg vs Tconv, but enriched at the core Treg signature loci that it upregulates. FoxP3 association correlates with heightened H3H27Ac looping, as ascertained by analysis of FoxP3-deficient Treg-like cells. There was marked asymmetry in the loci where FoxP3 associated at the enhancer- or the promoter-side of EPLs, with enrichment for different transcriptional cofactors. FoxP3 EPL intensity distinguished gene clusters identified by single-cell ATAC-seq as co-varying between individual Tregs, supporting a direct transactivation model for FoxP3 in determining Treg identity.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Yasukazu Nakahata ◽  
Yasumasa Bessho

Gene expression is known to be a stochastic phenomenon. The stochastic gene expression rate is thought to be altered by topological change of chromosome and/or by chromatin modifications such as acetylation and methylation. Changes in mechanical properties of chromosome/chromatin by soluble factors, mechanical stresses from the environment, or metabolites determine cell fate, regulate cellular functions, or maintain cellular homeostasis. Circadian clock, which drives the expression of thousands of genes with 24-hour rhythmicity, has been known to be indispensable for maintaining cellular functions/homeostasis. During the last decade, it has been demonstrated that chromatin also undergoes modifications with 24-hour rhythmicity and facilitates the fine-tuning of circadian gene expression patterns. In this review, we cover data which suggests that chromatin structure changes in a circadian manner and that NAD+is the key metabolite for circadian chromatin remodeling. Furthermore, we discuss the relationship among circadian clock, NAD+metabolism, and aging/age-related diseases. In addition, the interventions of NAD+metabolism for the prevention and treatment of aging and age-related diseases are also discussed.


2011 ◽  
Vol 120 (02) ◽  
pp. 101-109 ◽  
Author(s):  
W. Łuczyński ◽  
N. Wawrusiewicz-Kurylonek ◽  
A. Szypowska ◽  
E. Iłendo ◽  
A. Bossowski ◽  
...  

AbstractThere is increasing evidence that T-regulatory (Treg) cells could be used to prevent or cure autoimmune diseases including type 1 diabetes mellitus (T1DM). The aim of the present study was to verify the hypothesis that functional Treg cells can be generated from conventional T-cells separated from a small amount of peripheral blood of children with newly diagnosed T1DM (N=25).CD4+CD25- cells were cultured with Treg expander (CD3/CD28) and IL-2 for generating de novo Treg cells. The assessment of the expression of selected genes and proteins critical to Treg function and the proliferation assays were performed with the use of real-time RT-PCR and flow cytometry.After a 4-week stimulation with Treg expander and IL-2, the percentage of T-regulatory cells was significantly higher compared to the cells treated with medium alone (with no difference between diabetic and control children). However, we found some disturbances in the gene expression at mRNA level for molecules crucial for T-reg function. The induced Tregs from diabetic and control children were fully functional as assessed in proliferation assays.despite some disturbances at mRNA level in the critical gene expression, the suppressive properties of induced Treg cells from diabetic and control children were effective.


2017 ◽  
Vol 73 (8) ◽  
pp. 456-461
Author(s):  
Ewelina Bigoraj ◽  
Artur Rzeżutka

Hepatitis E virus (HEV) is a hepatovirus causing infections in humans and in many animal species. According to the current knowledge, HEV strains have been classified in the genus Orthohepevirus, family Hepeviridae, which encompasses strains belonging to one of seven virus genotypes. Genotypes 1 and 2 have only been found in humans, while genotypes 3 and 4 have been detected in humans, pigs, deer, rabbits and mongoose. The other HEV genotypes infect wild animals. However, the full spectrum of animal species being the natural reservoir of HEV has not been fully recognized. The clinical course of hepatitis in animals is asymptomatic, and infections do not cause significant losses in animal farming. Unlike in animals, infections in humans, and especially in pregnant women, can cause serious health problems. The identification of new virus strains in the animal reservoir and the possibility of transmission of some animal HEV strains to humans make the issue of public health protection and food safety even more important. This article provides an overview of data on the prevalence of HEV infections in animals and their impact on human and animal health


Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 539 ◽  
Author(s):  
Xiaohui Ju ◽  
Qiang Ding

Hepatitis E is an underestimated threat to public health, caused by the hepatitis E virus (HEV). HEV is the most common cause of acute viral hepatitis in the world, with no available direct-acting antiviral treatment. According to a recent WHO report, 20 million people become infected with HEV annually, resulting in 44,000 deaths. However, due to the scarcity of efficient in vitro cell culture systems for HEV, our knowledge of the life cycle of HEV is incomplete. Recently, significant progress has been made towards gaining a more comprehensive view of the HEV life cycle, as several in vitro culturing systems have been developed in recent years. Here, we review current knowledge and recent advances with regard to the HEV life cycle, with a particular focus on the assembly and release of viral particles. We also discuss the knowledge gaps in HEV assembly and release. Meanwhile, we highlight experimental platforms that could potentially be utilized to fill these gaps. Lastly, we offer perspectives on the future of research into HEV virology and its interaction with host cells.


2017 ◽  
Vol 55 ◽  
pp. 6-17 ◽  
Author(s):  
Aline S.B. Perazzio ◽  
José Salvador R. Oliveira ◽  
Vera L.P. Figueiredo ◽  
Maria de Lourdes L.F. Chauffaille

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 909
Author(s):  
Putu Prathiwi Primadharsini ◽  
Shigeo Nagashima ◽  
Hiroaki Okamoto

Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. While the transmission in developing countries is dominated by fecal-oral route via drinking contaminated water, the zoonotic transmission is the major route of HEV infection in industrialized countries. The discovery of new HEV strains in a growing number of animal species poses a risk to zoonotic infection. However, the exact mechanism and the determinant factors of zoonotic infection are not completely understood. This review will discuss the current knowledge on the mechanism of cross-species transmission of HEV infection, including viral determinants, such as the open reading frames (ORFs), codon usage and adaptive evolution, as well as host determinants, such as host cellular factors and the host immune status, which possibly play pivotal roles during this event. The pathogenesis of hepatitis E infection will be briefly discussed, including the special forms of this disease, including extrahepatic manifestations, chronic infection, and fulminant hepatitis in pregnant women.


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