Proteomic characterization of the natural history of chronic HBV infection revealed by tandem mass tag-based quantitative proteomics approach

Xun, Zhen; Yao, Xiaobao; Zhu, Chenggong; Ye, Yuchen; Wu, Songhang; Chen, Tianbin; Zeng, Yongbin; Lin, Caorui; Yang, Bin; Ou, Qishui; Liu, Can

doi:10.1016/j.mtbio.2022.100302

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…In addition, the treatment of RO7020531 triggered obvious immune activation in patients with CHB [ 113 , 114 , 115 ]. Moreover, recently developed TLR-8 agonists may contribute to the activation of PRRs present in the liver, and GS-9688 has been shown to promote the production of IL-12 and IL-18 from monocytes or DCs [ 116 , 117 , 118 ]. Furthermore, as cytokines such as IL-12 also contribute to NK cell activation, which have been demonstrated to kill both HBV-infected hepatocytes and HBV-specific CD8 + T cells, it is necessary to comprehensively evaluate the function of activated innate immunity in the process of HBV eradication.…”

Section: Progress In Hepatitis-b-specific Immunotherapymentioning

confidence: 99%

Advances in Immunotherapy for Hepatitis B

Wang

Wei

2022

Pathogens

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Hepatitis B virus (HBV) is a hepatotropic virus with the potential to cause chronic infection, and it is one of the common causes of liver disease worldwide. Chronic HBV infection leads to liver cirrhosis and, ultimately, hepatocellular carcinoma (HCC). The persistence of covalently closed circular DNA (cccDNA) and the impaired immune response in patients with chronic hepatitis B (CHB) has been studied over the past few decades. Despite advances in the etiology of HBV and the development of potent virus-suppressing regimens, a cure for HBV has not been found. Both the innate and adaptive branches of immunity contribute to viral eradication. However, immune exhaustion and evasion have been demonstrated during CHB infection, although our understanding of the mechanism is still evolving. Recently, the successful use of an antiviral drug for hepatitis C has greatly encouraged the search for a cure for hepatitis B, which likely requires an approach focused on improving the antiviral immune response. In this review, we discuss our current knowledge of the immunopathogenic mechanisms and immunobiology of HBV infection. In addition, we touch upon why the existing therapeutic approaches may not achieve the goal of a functional cure. We also propose how combinations of new drugs, and especially novel immunotherapies, contribute to HBV clearance.

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Section: Progress In Hepatitis-b-specific Immunotherapymentioning

confidence: 99%

Advances in Immunotherapy for Hepatitis B

Wang

Wei

2022

Pathogens

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“…Tandem mass tag (TMT)-based proteomics technology has the advantages of high throughput, high sensitivity, good reproducibility, low systematic bias, and low noise. Therefore, multiple studies have used this strategy to analyze disease-specific protein targets and understand the molecular mechanisms involved in various diseases [16,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

TMT-Based Proteomics Analysis of Senescent Nucleus Pulposus from Patients with Intervertebral Disc Degeneration

Zhang,

Li,

Yang

et al. 2023

IJMS

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Lower back pain, a leading cause of disability worldwide, is associated with intervertebral disc degeneration (IDD) in approximately 40% of cases. Although nucleus pulposus (NP) cell senescence is a major contributor to IDD, the underlying mechanisms remain unclear. We collected NP samples from IDD patients who had undergone spinal surgery. Healthy and senescent NP tissues (n = 3) were screened using the Pfirrmann grading system combined with immunohistochemistry, as well as hematoxylin and eosin, Safranin O, Alcian blue, and Masson staining. Differentially expressed proteins (DEPs) were identified using quantitative TMT-based proteomics technology. Bioinformatics analyses included gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein–protein interaction (PPI) analyses. In addition, immunofluorescence was used to verify protein expression. In total, 301 DEPs were identified in senescent NP tissues, including 92 upregulated and 209 downregulated proteins. In GO, DEPs were primarily associated with NF-kappaB transcription factor, extracellular regions, cellular protein metabolic processes, and post-translational protein modification. The enriched KEGG pathways included TGF-β, Wnt, RAP1, interleukin-17, extracellular matrix-receptor adhesion, and PI3K/Akt signaling pathways. PPI analysis demonstrated interactions between multiple proteins. Finally, immunofluorescence verified the expressions of MMP3, LUM, TIMP1, and CDC42 in senescent NP cells. Our study provides valuable insights into the mechanisms underlying senescent NP tissues in IDD patients. DEPs provide a basis for further investigation of the effects of senescent factors on IDD.

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“…However, current clinical practice sees only about one-third of patients with CHB responding to PegIFNα treatment ( 2 ). Although it is known that reciprocal interactions between HBV and the host contribute substantially to the efficacy of antiviral drugs, there have been relatively few studies to identify host genetic markers with potential prognostic value regarding whether patients may benefit from antiviral therapies ( 12 , 13 ). Single-nucleotide polymorphisms (SNPs) have been associated with individual disease susceptibility and differential treatment responses for many diseases ( 14 ), and the signal transducing activator of transcription 4 ( STAT4 ) rs7574865 allele is a reliable predictor of response to PegIFNα therapy in patients who are HBeAg positive ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B

Wang,

Lin,

Zhang

et al. 2023

Microbiol Spectr

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Objectives: Pegylated interferon alfa (PegIFNα) has limited efficacy in patients with chronic hepatitis B (CHB). Because single-nucleotide polymorphisms (SNPs) are known to confer disease susceptibility and influence treatment response, we aimed to identify novel tripartite motif-containing 22 (TRIM22) SNPs that were associated with therapeutic efficacy in patients with CHB after PegIFNα treatment. Samples from 107 patients with CHB were genotyped using Asian Screening Array gene chips. The related mechanisms of SNPs screened were explored through both cell experiments and RNA sequence methods. TRIM22 was the most upregulated upon stimulation with PegIFNα. Specifically, the SNP rs10838543 CC genotype in TRIM22 was found to be associated with the positive response to PegIFNα treatment. The SNP rs10838543 CC genotype in TRIM22 was more stable and more robustly inhibited hepatitis B virus (HBV) replication in HepAD38 cells compared to the TT genotype. Mechanistically, we showed that the cytokine-cytokine receptor interaction signaling pathway was significantly upregulated in HepAD38 cells stably expressing the SNP rs10838543 CC genotype of TRIM22 compared to the TT genotype after PegIFNα treatment and that the SNP rs10838543 CC genotype in TRIM22 enhanced PegIFNα-induced anti-HBV activity by inducing the secretion of IFNL1, CCL3, and CCL5. The SNP rs10838543 CC genotype in TRIM22 increased the secretion of the cytokines IFNL1, CCL3, and CCL5 from hepatocytes by regulating the cytokine-cytokine receptor interaction signaling pathway and was positively correlated with the PegIFNα-induced treatment response in patients with CHB. Our findings suggest that genotyping patients with CHB for the SNP rs10838543 in TRIM22 may be a useful biomarker to help physicians identify patients who are most likely to benefit from PegIFNα treatment. IMPORTANCE Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.

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Proteomic characterization of the natural history of chronic HBV infection revealed by tandem mass tag-based quantitative proteomics approach

Cited by 5 publications

References 46 publications

Advances in Immunotherapy for Hepatitis B

Advances in Immunotherapy for Hepatitis B

TMT-Based Proteomics Analysis of Senescent Nucleus Pulposus from Patients with Intervertebral Disc Degeneration

A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B

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