scholarly journals A genome-wide CRISPR screen identifies ZCCHC14 as a host factor required for hepatitis B surface antigen production

2019 ◽  
Author(s):  
Anastasia Hyrina ◽  
Christopher Jones ◽  
Darlene Chen ◽  
Scott Clarkson ◽  
Nadire Cochran ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Genome Wide ◽  
A Genome ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Crispr Screen ◽  
Novel Host ◽  
Circulating Levels

GRAPHICAL ABSTRACTSUMMARYA hallmark of chronic hepatitis B virus (CHB) infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A novel small molecule RG7834 has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase protein 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential novel host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identified novel factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients.

scholarly journals A Genome-wide CRISPR Screen Identifies ZCCHC14 as a Host Factor Required for Hepatitis B Surface Antigen Production

Cell Reports ◽  
2019 ◽  
Vol 29 (10) ◽  
pp. 2970-2978.e6 ◽  
Author(s):  
Anastasia Hyrina ◽  
Christopher Jones ◽  
Darlene Chen ◽  
Scott Clarkson ◽  
Nadire Cochran ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Host Factor ◽  
Antigen Production ◽  
Genome Wide ◽  
A Genome ◽  
Crispr Screen

scholarly journals Serum immunoconglutinin titers during acute and chronic hepatitis B virus infection

1980 ◽  
Vol 28 (3) ◽  
pp. 842-845
Author(s):  
G M Makhdoomi ◽  
M L Tiku ◽  
K R Beutner ◽  
P L Ogra
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Acute And Chronic Hepatitis ◽  
Surface Antibody

Sera from 99 chronic hepatitis B surface antigen carriers, 12 individuals with acute type B hepatitis, 26 hepatitis B surface antibody-seropositive subjects, and 50 hepatitis B surface antigen, hepatitis B surface antibody-seronegative subjects were evaluated for the presence of serum imunoconglutinis (IKs). The mean serum IK titers of hepatitis B surface antibody-seropositive and hepatitis B virus-seronegative subjects wre 5.3 and 4.9, respectively. The IK titers of subjects with acute and chronic hepatitis B virus infections were 215.4 and 19.1, respectively. These groups also manifested IK titers greater than or equal to > 16 significantly (P < 0.005) more often than controls did. Among chronic hepatitis B surface antigen carriers, high IK titers were associated with low levels of hepatitis B surface antigen. IK titers of individuals chronically infected with hepatitis B virus and having the rheumatoid factor were similar to those of individuals without the rheumatoid factor. Elevated IK titers represent a physiological autoimmune response and may indicate the presence of immune complexes in acute and chronic hepatitis B virus infection.

scholarly journals Comparison of Three Luminescent Immunoassays for Hepatitis B Virus Surface Antigen Quantification during the Natural History of Chronic Hepatitis B Virus Infection

2014 ◽  
Vol 21 (11) ◽  
pp. 1521-1527 ◽  
Author(s):  
Xiao-Dong Cheng ◽  
Liu-Wei Song ◽  
Lin-Lin Fang ◽  
Lin Yang ◽  
Yong Wu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Serum Samples ◽  
Virus Surface ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACTHepatitis B surface antigen (HBsAg) quantification has garnered attention because of its high predictive value in determining treatment responses. The HBsAg quantification assays, such as Architect and Elecsys, are commercially available, and more assays are in development. We aimed to compare the results of the Architect and Elecsys assays with those of a new assay, WTultra. The WTultra HBsAg assay is a sandwich chemiluminescent microplate enzyme immunoassay and provides an alternative choice which is more cost-effective and potentially applicable in developing or resource-constrained countries and areas. A total of 411 serum samples were collected from patients during various phases of chronic hepatitis B (CHB) infection. The samples were assessed using the three assays, and the results were compared and analyzed. The results for the Architect, Elecsys, and WTultra assays were well correlated according to the overall results for the samples (correlation coefficients,rArchitect versus WTultra= 0.936,rArchitect versus Elecsys= 0.952, andrWTultra versus Elecsys= 0.981) and the various infection phases (rArchitect versus WTultraranging from 0.67 to 0.975,rArchitect versus Elecsysranging from 0.695 to 0.982, andrWTultra versus Elecsysranging from 0.877 to 0.99). Additionally, consistent results were observed according to genotype (genotype B:rArchitect versus WTultra= 0.976,rArchitect versus Elecsys= 0.978, andrWTultra versus Elecsys= 0.979; genotype C:rArchitect versus WTultra= 0.950,rArchitect versus Elecsys= 0.963, andrWTultra versus Elecsys= 0.981) and hepatitis B virus (HBV) DNA levels (rArchitect= 0.540,rWTultra= 0.553, andrElecsys= 0.580). In conclusion, the Elecsys and WTultra assays were well correlated with the Architect assay, irrespective of the CHB infection phase or genotype. All of these assays are reliable for HBsAg quantification.

scholarly journals A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Kiruthika ◽  
Ruchika Bhat ◽  
Rozaleen Dash ◽  
Anurag S. Rathore ◽  
Perumal Vivekanandan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Small Molecules ◽  
Small Molecule ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Resonance Spectroscopy ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Dynamics Simulations

AbstractChronic hepatitis B virus (HBV) infection is a global problem. The loss of hepatitis B surface antigen (HBsAg) in serum is a therapeutic end point. Prolonged therapy with nucleoside/nucleotide analogues targeting the HBV-polymerase may lead to resistance and rarely results in the loss of HBsAg. Therefore, inhibitors targeting HBsAg may have potential therapeutic applications. Here, we used computational virtual screening, docking, and molecular dynamics simulations to identify potential small molecule inhibitors against HBsAg. After screening a million molecules from ZINC database, we identified small molecules with potential anti-HBV activity. Subsequently, cytotoxicity profiles and anti-HBV activities of these small molecules were tested using a widely used cell culture model for HBV. We identified a small molecule (ZINC20451377) which binds to HBsAg with high affinity, with a KD of 65.3 nM, as determined by Surface Plasmon Resonance spectroscopy. Notably, the small molecule inhibited HBsAg production and hepatitis B virion secretion (10 μM) at low micromolar concentrations and was also efficacious against a HBV quadruple mutant (CYEI mutant) resistant to tenofovir. We conclude that this small molecule exhibits strong anti-HBV properties and merits further testing.

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