scholarly journals Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection

2007 ◽  
Vol 81 (8) ◽  
pp. 4215-4225 ◽  
Author(s):  
Carolina Boni ◽  
Paola Fisicaro ◽  
Caterina Valdatta ◽  
Barbara Amadei ◽  
Paola Di Vincenzo ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Cell Dysfunction ◽  
B Virus ◽  
T Cell Dysfunction ◽  
Chronic Hbv

ABSTRACT Dysfunctional CD8+ T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T-cell dysfunction and on its reversibility through the blocking of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus-specific T cells were detected mainly in patients with lower levels of viremia. These HBV-specific CD8+ T cells expressed PD-1, and their function was improved by the blocking of PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD-1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies.

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

2018 ◽  
Vol 56 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Yu-Gang Wang ◽  
Dong-Hui Zheng ◽  
Min Shi ◽  
Xi-Ming Xu
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
T Cell ◽  
Virus Infection ◽  
Hbv Infection ◽  
Differentially Expressed ◽  
Chronic Hbv Infection ◽  
Cell Dysfunction ◽  
T Cell Dysfunction ◽  
Chronic Hbv

BackgroundT cell dysfunction occurs in many diseases, especially in chronic virus infection and cancers. However, up to now, little is known on the distinctions in T cell exhaustion between cancer and chronic virus infection. The objective of this study is to explore the transcriptional similarities and differences in exhausted CD8 +T cell between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).MethodsRNA sequencing was performed to compare the transcriptome of CD8 +T cells isolated from healthy donors’ blood, tumour tissues of patients with HCC and chronic HBV infected HCC patients’ paracancerous tissues. DESeq2 algorithm was used to determine differentially expressed genes. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted for in-depth analysis of these differentially expressed genes.ResultsA total number of 2109 and 2203 genes were differentially expressed in patients with chronic HBV infection and HCC, respectively. Comparing these two groups of differentially deregulated genes, we found that nearly half of them were shared, and these shared genes were further classified into several functional categories, such as metabolic process, binding and intracellular organelle. KEGG analysis revealed that these shared deregulated genes were involved in many important pathways such as Parkinson’s disease, oxidative phosphorylation and messenger RNA surveillance. Interestingly, we reported that chronic HBV infection specific deregulated genes were mainly enriched in graft versus host disease, allograft rejection, phenylalanine, tyrosine and tryptophan biosynthesis pathways. Whereas, HCC-specific deregulated genes were highly enriched in oxidative phosphorylation, thyroid cancer and endometrial cancer pathways.ConclusionOur study demonstrated that T cell dysfunction associated with HCC and chronic HBV infection shares high similarities, however, each possesses its own features in terms of specific genes and signalling pathways. Uncovering the differences of T cells dysfunction would facilitate our understanding the diseases pathogenesis and developing innovative therapies in the future.

scholarly journals Dynamic, Helminth-Induced Immune Modulation Influences the Outcome of Acute and Chronic Hepatitis B Virus Infection

2019 ◽  
Vol 221 (9) ◽  
pp. 1448-1461
Author(s):  
Eva Loffredo-Verde ◽  
Sonakshi Bhattacharjee ◽  
Antje Malo ◽  
Julia Festag ◽  
Anna D Kosinska ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Schistosome Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Ifn Γ ◽  
Chronic Hbv

Abstract Background Chronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood. Methods We used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection. Results Although liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-γ secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the TH1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-γ-deficient or in TH2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV. Conclusions Thus, schistosome-induced IFN-γ had a prominent antiviral effect that outcompeted immunosuppressive effects of TH2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity.

scholarly journals Interleukin 21 Reinvigorates the Antiviral Activity of Hepatitis B Virus (HBV)–Specific CD8+ T Cells in Chronic HBV Infection

2018 ◽  
Vol 219 (5) ◽  
pp. 750-759 ◽  
Author(s):  
Libo Tang ◽  
Chengcong Chen ◽  
Xueping Gao ◽  
Wanyue Zhang ◽  
Xin Yan ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Cd8 T Cells ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Interleukin 21

scholarly journals Hepatitis B Virus Demethylates PD-1 and Modulates the Changes of the Tumor Microenvironment in Hepatocellular Carcinoma Patients

2021 ◽  
Author(s):  
Weiguang Lian ◽  
Ruixue Lai ◽  
Jianhua Wu ◽  
Jingjing Zhang ◽  
Shengchao Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
T Cells ◽  
Hepatitis B Virus ◽  
Tumor Microenvironment ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

Abstract Background: Hepatitis B virus (HBV) constitutes a major global health burden. Previously study has found the expression of programmed cell death 1 (PD-1) is up-regulated during the chronic HBV infection. However, the mechanism of how HBV infection modulates the expression of PD-1 on CD8+T cells are not well understood. In the present study, we aimed to analyzed the role of DNA methylation in regulating the expression of PD-1 on CD8+T cells during HBV infection, we also aimed to evaluate the HBV induced changes of tumor microenvironment (TME).Methods: The methylation microarray was used to assess the profile changes of gene methylation upon chronic HBV infection. CD8+T cells were separated from peripheral blood of health volunteers and HCC patients including HBV related HCC (HBV-HCC) and non-viral HCC. The immune microenvironments of hepatocellular carcinoma (HCC) was interrogated by using Immunofluorescence staining. The PD-1 expression of CD8+T cells from peripheral blood were examined by western blot and flow cytometry. T cells function was determined by cytokine measurement. Sequenom MassARRAY platform was used to detected the DNA methylation status of PD-1 promoter.Results: HBV could drive 413 genes methylated while 3,023 genes including PD-1 demethylated, the reduced PD-1 expression and increased PD-1 demethylation was proved in HBV-HCC tissue. The subsequent analysis indicate that the expression of PD-1 differed by stages of HBV infection, it reduced on the cell membrane of HBV-transfected CD8+T cells upon transient HBV plasmid transfection which might mimic acute HBV infection, while upregulated on the HBV specific CD8+T cells by demethylation during chronic HBV infection. Interferon-gamma increased in the medium of HBV transfected CD8+T cells and interleukin-10 increased in the blood of chronic HBV infection patients. Increased tumor associated macrophage (TAM) cells and T regulatory cells (Tregs) invasion was identified in HBV-HCC tissue when compared with those from non-viral HCC tissue Conclusion: Our data suggested that the expression of PD-1 varies upon the stage of HBV infection, chronic HBV infection could drove the TME more immunosuppressive through PD-1 demethylation related CD8+T cells exhaustion as well as promotion of invaded Treg and TAM cells thereby to attenuating therapy of immune checkpoint inhibitors.

scholarly journals Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

2021 ◽  
Vol 10 (13) ◽  
pp. 2926
Author(s):  
Sirinart Sirilert ◽  
Theera Tongsong
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnancy Outcomes ◽  
Natural Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Adverse Pregnancy ◽  
The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

scholarly journals G‐to‐A Hypermutation in Hepatitis B Virus (HBV) and Clinical Course of Patients with Chronic HBV Infection

2009 ◽  
Vol 199 (11) ◽  
pp. 1599-1607 ◽  
Author(s):  
Chiemi Noguchi ◽  
Michio Imamura ◽  
Masataka Tsuge ◽  
Nobuhiko Hiraga ◽  
Nami Mori ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv
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