scholarly journals Identification and characterization of lncRNA AP000253 in occult hepatitis B virus infection

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Qingqin Hao ◽  
Zheng Wang ◽  
Qinghui Wang ◽  
Bo Chen ◽  
Huizhong Qian ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Plasma Level ◽  
Hepatitis B ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Hbv Infection ◽  
Occult Hbv ◽  
Potential Biomarker ◽  
B Virus ◽  
Liver Tissues

Abstract Background Recent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear. Methods The plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines. Results Among candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines. Conclusions AP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.

scholarly journals Hepatitis B Virus Replication Induces Methylation of both Host and Viral DNA

2010 ◽  
Vol 84 (9) ◽  
pp. 4321-4329 ◽  
Author(s):  
Perumal Vivekanandan ◽  
Hubert Darius-J Daniel ◽  
Rajesh Kannangai ◽  
Francisco Martinez-Murillo ◽  
Michael Torbenson
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Replication ◽  
Cell Lines ◽  
Natural Infection ◽  
Cpg Islands ◽  
Hbv Infection ◽  
Viral Dna ◽  
B Virus

ABSTRACT Control of viral replication is a major therapeutic goal to reduce morbidity and mortality from chronic hepatitis B virus (HBV) infection. Recently, methylation has been identified as a novel host defense mechanism, and methylation of viral DNA leads to downregulation of HBV gene expression. To better understand the mechanisms of HBV methylation, cell lines were exposed to HBV using a model system that mimics natural infection and the expression of host DNA methyltransferase genes (DNMTs) was measured. DNMT1, DNMT2, and DNMT3 were all significantly upregulated in response to HBV. DNMT3 was further studied because of its known role in the de novo methylation of DNA. Cotransfection experiments with full-length HBV and DNMT3 led to the downregulation of viral protein and pregenomic RNA production. To investigate whether the upregulation of DNMTs could also have an effect on the methylation of host DNA, cell lines were exposed to HBV in two independent model systems, one that mimics natural infection and a second model with temporary transfection. Host DNA methylation was measured by DNA microarray analysis. Increased methylation of host CpG islands was detected in both experimental systems. Two CpG islands, corresponding to genes SUFU and TIRAP, were selected, and the downregulation of these genes in hepatocellular carcinomas was confirmed. In conclusion, hepatocytes respond to HBV infection by upregulating DNMTs. The DNMTs methylate viral DNA, leading to decreased viral gene expression and decreased viral replication. However, virus-induced overexpression of DNMTs also leads to methylation of host CpG islands.

Chemokine Expression Profiles of Human Hepatoma Cell Lines Mediated by Hepatitis B Virus X Protein

2015 ◽  
Vol 22 (2) ◽  
pp. 393-399 ◽  
Author(s):  
Di-Yi Wang ◽  
Li-Ping Zou ◽  
Xiao-Jia Liu ◽  
Hong-Guang Zhu ◽  
Rong Zhu
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Lines ◽  
Expression Profiles ◽  
Hepatoma Cell ◽  
Human Hepatoma ◽  
X Protein ◽  
Human Hepatoma Cell ◽  
Hepatoma Cell Lines ◽  
B Virus

A new method of concentrating hepatitis B virus (HBV) DNA and HBV surface antigen: an application of the method to the detection of occult HBV infection

Vox Sanguinis ◽  
2008 ◽  
Vol 95 (3) ◽  
pp. 174-180 ◽  
Author(s):  
K. Satoh ◽  
A. Iwata-Takakura ◽  
A. Yoshikawa ◽  
Y. Gotanda ◽  
T. Tanaka ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
New Method ◽  
Occult Hbv Infection ◽  
Occult Hbv ◽  
B Virus

Hepatitis B Virus e Antigen Downregulates Cytokine Production in Human Hepatoma Cell Lines

2010 ◽  
Vol 23 (5) ◽  
pp. 467-476 ◽  
Author(s):  
Shuang Wu ◽  
Tatsuo Kanda ◽  
Fumio Imazeki ◽  
Makoto Arai ◽  
Yutaka Yonemitsu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Lines ◽  
Cytokine Production ◽  
Hepatoma Cell ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Hepatoma Cell Lines ◽  
B Virus

scholarly journals Hepatitis B Virus-Encoded MicroRNA Controls Viral Replication

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Xi Yang ◽  
Hongfeng Li ◽  
Huahui Sun ◽  
Hongxia Fan ◽  
Yaqi Hu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Persistent Infection ◽  
Hepatoma Cell ◽  
Hbv Infection ◽  
Dependent Manner ◽  
Dna Virus ◽  
Hbv Replication ◽  
B Virus ◽  
Self Replication

ABSTRACT MicroRNAs (miRNAs) are a class of small, single-stranded, noncoding, functional RNAs. Hepatitis B virus (HBV) is an enveloped DNA virus with virions and subviral forms of particles that lack a core. It was not known whether HBV encodes miRNAs. Here, we identified an HBV-encoded miRNA (called HBV-miR-3) by deep sequencing and Northern blotting. HBV-miR-3 is located at nucleotides (nt) 373 to 393 of the HBV genome and was generated from 3.5-kb, 2.4-kb, and 2.1-kb HBV in a classic miRNA biogenesis (Drosha-Dicer-dependent) manner. HBV-miR-3 was highly expressed in hepatoma cell lines with an integrated HBV genome and HBV+ hepatoma tumors. In patients with HBV infection, HBV-miR-3 was released into the circulation by exosomes and HBV virions, and HBV-miR-3 expression had a positive correlation with HBV titers in the sera of patients in the acute phase of HBV infection. More interestingly, we found that HBV-miR-3 represses HBsAg, HBeAg, and replication of HBV. HBV-miR-3 targets the unique site of the HBV 3.5-kb transcript to specifically reduce HBc protein expression, levels of pregenomic RNA (pgRNA), and HBV replication intermediate (HBV-RI) generation but does not affect the HBV DNA polymerase level, thus suppressing HBV virion production (replication). This may explain the low levels of HBV virion generation with abundant subviral particles lacking core during HBV replication, which may contribute to the development of persistent infection in patients. Taken together, our findings shed light on novel mechanisms by which HBV-encoded miRNA controls the process of self-replication by regulating HBV transcript during infection. IMPORTANCE Hepatitis B is a liver infection caused by the hepatitis B virus (HBV) that can become a long-term, chronic infection and lead to cirrhosis or liver cancer. HBV is a small DNA virus that belongs to the hepadnavirus family, with virions and subviral forms of particles that lack a core. MicroRNA (miRNA), a small (∼22-nt) noncoding RNA, was recently found to be an important regulator of gene expression. We found that HBV encodes miRNA (HBV-miR-3). More importantly, we revealed that HBV-miR-3 targets its transcripts to attenuate HBV replication. This may contribute to explaining how HBV infection leads to mild damage in liver cells and the subsequent establishment/maintenance of persistent infection. Our findings highlight a mechanism by which HBV-encoded miRNA controls the process of self-replication by regulating the virus itself during infection and might provide new biomarkers for diagnosis and treatment of hepatitis B.

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