Complement C4a inhibits the secretion of hepatitis B virus screened by surface‐enhanced laser desorption ionization time‐flight mass spectrometry‐based ProteinChip analysis

Song, Yanan; Zhang, Gui-biao; Hu, Xueqing; Lu, Yi‐Yu; Zhao, Yu; Yang, Yang; Yang, Ye; Zhang, Yongyu; Hu, Yiyang; Su, Shi‐Bing

doi:10.1002/prca.201500009

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…Previous studies showed that IFN could enhance expression of C2, C4, complement factor B, complement factor H, C1 inhibitor and C4‐binding protein 27,37 . Moreover, inhibition of C4a could lead to increase of HBV‐DNA secretion by HepG2.2.15 cells and inhibition of complement factor B could increase the susceptibility of Huh7.5 cells to ZKV virus, suggesting an anti‐virus effect byC4 and complement factor B 38,39 . Similarly, in our present study, IFN was found to promote C2 expression in HepG2.2.15 cells and C2 could enhance the anti‐virus effect of IFN in HepG2.2.15 cells.…”

Section: Discussionsupporting

confidence: 85%

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Ning

Zhen

et al. 2020

Journal of Viral Hepatitis

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Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat‐sen University between January 2018 and January 2020. HepG2.2.15 and HepG2‐NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN‐treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2‐overexpressing or C2‐silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT‐qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV‐DNA was measured by RT‐qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti‐virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38‐MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.

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Section: Discussionsupporting

confidence: 85%

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Ning

Zhen

et al. 2020

Journal of Viral Hepatitis

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“…The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation (MIM: 120 810). Song et al found the important role of complement C4A in inhibiting HBV DNA secretion in chronic HBV 36 . Our GSEA of C4A showed that C4A was involved in the immune response (Figure ).…”

Section: Discussionmentioning

confidence: 61%

Transcriptome‐wide association study for persistent hepatitis B virus infection and related hepatocellular carcinoma

Han

Chen

Wang

et al. 2020

Liver International

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Background & Aims Previous genome‐wide association studies (GWAS) have identified multiple susceptible variants associated with persistent hepatitis B virus (HBV) infection. However, most of these variants are located in the noncoding regions, which make it difficult to determine the effective genes underlying these associations. We performed a two‐stage study, in the first stage we integrated RNA sequencing data of liver tissues and high‐density genotyping data from the Genotype‐Tissue Expression (GTEx) project with our previous GWAS data to conduct a transcriptome‐wide association study (TWAS) on HBV infection. Firstly, the cis‐heritable genes were screened by a genetic relatedness matrix of genome‐wide complex trait analysis (GCTA) from GTEx data. Then, the genetic expression of 2587 cis‐heritable genes was predicted by restricted maximum likelihood (REML) of genome‐wide efficient mixed‐model association (GEMMA) in our GWAS data with 951 HBV carrier cases and 937 HBV cleared controls. Next, we investigated the associations between predictive expression levels and persistent HBV infection risk. Gene set enrichment analysis (GSEA) was applied to infer the function of the identified genes. To identify the causal single nucleotide polymorphisms (SNPs) of HBV infection risk, we conducted the expression quantitative trait loci (eQTL)‐based stepwise logistic regression analysis in the regions around 1 Mb of these genes and validated the association between 994 health controls and 994 HBV‐persistent infection cases by genotyping experiment. In the second stage, 1538 HBV‐related hepatocellular carcinoma (HCC) cases and 1465 persistent HBV infection controls were collected to determine the effect of these variants on HBV‐related HCC as well, which were examined by the additive model in logistic regression analysis. We identified seven genes associated with HBV infection. In the classic human leukocyte antigen (HLA) region, three novel genes BAK1, HLA‐DOB and C4A (Z range from −3.95 to −3.64, P range from 7.84 × 10−5 to 2.00 × 10−4), as well as two genes (HLA‐DPA1 and HLA‐DPB1) were reported by previous GWAS. In the non‐HLA region, immune related at newly identified loci, PARP9 (Z = 3.69, P = 2.20 × 10−4) at 3q21.1. At 22q11.21, we identified TMEM191A (Z = 3.55, P = 3.80 × 10−4) as a target gene in addition to the reported non‐cis‐heritable gene UBE2L3. After further stepwise logistic regression analysis and validation, we identified eight variants independently associated with persistent HBV infection. Among those variants, the additive model showed that two SNPs associated with HBV‐related HCC risk (rs9272714 and rs9394194, OR range from 1.20 to 1.25, P range from 1.19 × 10−4 to 3.97 × 10−4). By integrating transcriptome data, our study not only identified new susceptibility loci of persistent HBV infection but also determined the potential target genes at reported loci, which provided insight into the genetic aetiology of persistent HBV infection and related HCC.

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“…Hepatic proteins were extracted and quantified by BCA assay kit (Boster, Wuhan, China). The experiment was constructed as previously published method [ 13 ]. Briefly, equal amounts of proteins were electrophoresed andelectrotransfered.…”

Section: Methodsmentioning

confidence: 99%

Metabolomic mechanisms of gypenoside against liver fibrosis in rats: An integrative analysis of proteomics and metabolomics data

et al. 2017

Self Cite

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AimsTo investigate mechanisms and altered pathways of gypenoside against carbon tetrachloride (CCl4)-induced liver fibrosis based on integrative analysis of proteomics and metabolomics data.MethodsCCl4-induced liver fibrosis rats were administrated gypenoside. The anti-fibrosis effects were evaluated by histomorphology and liver hydroxyproline (Hyp) content. Protein profiling and metabolite profiling of rats liver tissues were examined by isobaric tags for relative and absolute quantitation (iTRAQ) approach and gas chromatography-mass spectrometer (GC-MS) technology. Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data. The levels of some key proteins in altered pathways were determined by western blot.ResultsHistopathological changes and Hyp content in gypenoside group had significant improvements (P<0.05). Compared to liver fibrosis model group, we found 301 up-regulated and 296 down-regulated proteins, and 9 up-regulated and 8 down-regulated metabolites in gypenoside group. According to integrative analysis, some important pathways were found, including glycolysis or gluconeogenesis, fructose and mannose metabolism, glycine, serine and threonine metabolism, lysine degradation, arginine and proline metabolism, glutathione metabolism, and sulfur metabolism. Furthermore, the levels of ALDH1B1, ALDH2 and ALDH7A1 were found increased and restored to normal levels after gypenoside treated (P<0.05).ConclusionsGypenoside inhibited CCl4-induced liver fibrosis, which may be involved in the alteration of glycolysis metabolism and the protection against the damage of aldehydes and lipid peroxidation by up-regulating ALDH.

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Complement C4a inhibits the secretion of hepatitis B virus screened by surface‐enhanced laser desorption ionization time‐flight mass spectrometry‐based ProteinChip analysis

Abstract: The present study implied the important role of complement C4a in inhibiting the HBV DNA secretion in CHB.

Cited by 4 publications

References 27 publications

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Transcriptome‐wide association study for persistent hepatitis B virus infection and related hepatocellular carcinoma

Metabolomic mechanisms of gypenoside against liver fibrosis in rats: An integrative analysis of proteomics and metabolomics data

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