Hepatitis B Virus (HBV) Surface Antigen Interacts with and Promotes Cyclophilin A Secretion: Possible Link to Pathogenesis of HBV Infection

ABSTRACT Cyclophilin A (CypA), predominantly located intracellularly, is a multifunctional protein. We previously reported decreased CypA levels in hepatocytes of transgenic mice expressing hepatitis B virus (HBV) surface antigen (HBsAg). In this study, we found that expression of HBV small surface protein (SHBs) in human hepatoma cell lines specifically triggered CypA secretion, whereas SHBs added extracellularly to culture medium did not. Moreover, CypA secretion was not promoted by the expression of a secretion deficient SHBs mutant, suggesting a close association between secretion of CypA and SHBs. Interaction between CypA and SHBs was observed by using coimmunoprecipitation and glutathione S-transferase pull-down assays. Hydrodynamic injection of the SHBs expression construct into C57BL/6J mice resulted in increased serum CypA levels and ALT/AST levels, as well as the infiltration of inflammatory cells surrounding SHBs-positive hepatocytes. The inflammatory response and serum ALT/AST level were reduced when the chemotactic effect of CypA was inhibited by cyclosporine and anti-CD147 antibody. Furthermore, higher serum CypA levels were detected in chronic hepatitis B patients than in healthy individuals. In HBV patients who had received liver transplantation, serum CypA levels declined dramatically after the loss of HBsAg as a consequence of liver transplantation. Taken together, these results indicate that expression and secretion of SHBs can promote CypA secretion, which may contribute to the pathogenesis of HBV infection.

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Development and evaluation of an in-house ELISA to detect hepatitis B virus surface antigen in resource-limited settings

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v39i2.19644 ◽

2014 ◽

Vol 39 (2) ◽

pp. 65-68 ◽

Cited By ~ 2

Author(s):

K Fatema ◽

S Tabassum ◽

A Nessa ◽

M Jahan

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hbv Infection ◽

Health Concern ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Surface ◽

B Virus ◽

Commercial Kits ◽

Checkerboard Titration

Hepatitis B virus (HBV) infection is of global public health concern. Among various serological tests used for the diagnosis and screening of HBV infection, the enzyme-linked immunosorbent assay (ELISA) to detect hepatitis B surface antigen (HbsAg) is most widely used. The present study was designed to develop and standardize a cost effective in-house ELISA for the detection of HbsAg and compare its performance with two established commercial kits. The concentrations of coating antibody, conjugates and sera were fixed by checkerboard titration. Using known HBsAg positive and negative sera, four different concentrations (1, 0.5, 0.25 and 0.125 ?g/well) of coating anti-HBs were applied. Similarly, serial dilutions of patients sera (1 in 2, 1 in 3, 1 in 5 and 1 in 9) and conjugates (1 in 2, 1 in 3, 1 in 5, 1 in 9 and 1 in 17) were evaluated by checkerboard titration. The optimal concentration of coating antibody was determined at 0.25 ?g/well and 1 in 9 dilution for both conjugates and sera. The performance comparison of our in-house ELISA showed excellent correlation with two commercial kits (Pearson 0.957, P=0.001 for monoclonal antibody coated kit and Pearson 0.929, P=0.000 for polyclonal antibody coated kit) when OD values were compared. All commercial kit proven positive samples was positive while all negative samples were negative with the in-house ELISA resulting in 100% sensitivity and specificity. The results of our study demonstrated that our inhouse ELISA for detection of HBsAg was equally as sensitive and specific as two well-known commercial kits. Thus, this system may be a useful tool for diagnostic and screening purposes, as well as outbreak investigations. DOI: http://dx.doi.org/10.3329/bmrcb.v39i2.19644 Bangladesh Med Res Counc Bull 2013; 39: 65-68

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Baseline Quantitative Hepatitis B Core Antibody Titer Is a Predictor for Hepatitis B Virus Infection Recurrence After Orthotopic Liver Transplantation

Frontiers in Immunology ◽

10.3389/fimmu.2021.710528 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bin Lou ◽

Guanghua Ma ◽

Feifei LV ◽

Quan Yuan ◽

Fanjie Xu ◽

...

Keyword(s):

Liver Transplantation ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Median Time ◽

Orthotopic Liver Transplantation ◽

Cox Regression ◽

Hbv Infection ◽

Hbsag Loss ◽

Kaplan Meier ◽

B Virus

ObjectiveHepatitis B virus (HBV) reinfection is a serious complication that arise in patients who undergo hepatitis B virus related liver transplantation. We aimed to use biomarkers to evaluate the HBV reinfection in patients after orthotopic liver transplantation.MethodsSeventy-nine patients who underwent liver transplantation between 2009 and 2015 were enrolled, and levels of biomarkers were analyzed at different time points. Cox regression and receiver operating characteristic (ROC) curves of different markers at baseline were used to analyze sustained hepatitis B surface antigen (HBsAg) loss. The Kaplan-Meier method was used to compare the levels of the biomarkers.ResultsAmong the 79 patients, 42 sustained HBsAg loss with a median time of 65.2 months (12.0-114.5, IQR 19.5) after liver transplantation and 37 patients exhibited HBsAg recurrence with a median time of 8.8 (0.47-59.53, IQR 19.47) months. In the ROC curve analysis, at baseline, 4.25 log10 IU/mL qHBcAb and 2.82 log10 IU/mL qHBsAg showed the maximum Youden’s index values with area under the curves (AUCs) of 0.685and 0.651, respectively. The Kaplan-Meier method indicated that qHBsAg and quantitative antibody against hepatitis B core antigen (qHBcAb) levels in the two groups were significantly different (p = 0.031 and 0.006, respectively). Furthermore, the Cox regression model confirmed the predictive ability of qHBcAb at baseline (AUC = 0.685).ConclusionLower pretransplantation qHBcAb is associated with HBV infection. The baseline concentration of qHBcAb is a promising predictor for the recurrence of HBV in patients undergoing liver transplantation and can be used to guide antiviral treatment for HBV infection.

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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 ◽

10.1111/j.1423-0410.2008.01091.x ◽

2008 ◽

Vol 95 (3) ◽

pp. 174-180 ◽

Cited By ~ 15

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

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Hepatitis B Virus-Encoded MicroRNA Controls Viral Replication

Journal of Virology ◽

10.1128/jvi.01919-16 ◽

2017 ◽

Vol 91 (10) ◽

Cited By ~ 31

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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Seroprevalence of Hepatitis B Virus among antenatal clinic attendees in Gamawa Local Government Area, Bauchi State, Nigeria

10.21203/rs.2.10126/v1 ◽

2019 ◽

Author(s):

Garba Umar Mustapha ◽

Abdulrasul Ibrahim ◽

Muhammad Shakir Balogun ◽

Chukwuma David Umeokonkwo ◽

Aisha Indo Mamman

Keyword(s):

Hepatitis B Virus ◽

Local Government ◽

Hepatitis B ◽

Pregnant Women ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Local Government Area ◽

Hbv Infection ◽

Risk Of Death ◽

B Virus

Abstract Background: Hepatitis B is a potentially life-threatening liver infection and a major global health problem. It causes chronic infection and puts people at high risk of death from cirrhosis and liver cancer. WHO estimated 257 million people are living with hepatitis B virus (HBV) infection and in 2015 alone HBV resulted in to 887,000 deaths globally. We determined the prevalence and associated factors of hepatitis B virus infection among Antenatal Care (ANC) attendees in Gamawa Local Government Area, Bauchi State. Methods: We conducted a descriptive cross-sectional, health facility-based study between March and April 2018. We used systematic random sampling technique to recruit 210 pregnant women aged 15-49 years. With a structured questionnaire, we interviewed the respondents and collected blood sample to test for hepatitis B surface antigen. We calculated frequencies, means, proportions, and tested for associations using Epi Info 7.2 and Microsoft Excel. Results: The mean age of respondents was 24.5 ± 6.0 years; 53.3% of whom were younger than 25 years. All were married, 87.1% had no formal education and up to 90.5% were employed. Overall, 6.7% tested positive for HBsAg; women aged ≥35 years had the highest prevalence (10.5%). None with tertiary education tested positive and women married before 18 years had 6.5% prevalence. Conclusions: The prevalence of HBsAg among pregnant women in Gamawa LGA was 6.7% which is quite lower than the national prevalence reported. We recommended improved surveillance of HBV infection and screening of women attending ANC. Keywords: Hepatitis B virus, Hepatitis B Surface antigen, Prevalence, Pregnancy, Health facilities, Hepatitis B

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