scholarly journals Presence of sodium taurocholate co-transporting polypeptide and Hepatitis B replication marker on placenta: Another home for the virus

2022 ◽  
Author(s):  
Garima Garg ◽  
Meenu MN ◽  
Kajal Patel ◽  
Shashank Purwar ◽  
Sramana Mukhopadhyay ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B ◽  
Cellular Proliferation ◽  
Sodium Taurocholate ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Control Group ◽  
Cytoplasmic Staining ◽  
Hbv Replication ◽  
Significant Difference

Background: The role of sodium taurocholate co-transporting polypeptide (NTCP), in facilitating the binding of Hepatitis B virus (HBV) on surface of hepatocytes is well documented. Expression of NTCP in extra hepatic cells may make these cells susceptible to HBV infection and support cellular proliferation akin to hepatocytes. Placental replication of HBV is not well explored. In this study we have assessed the expression of NTCP and HBV replication markers (HBeAg, HBcAg, and HBV DNA) in placental cells, to investigate if these cells act as host for HBV. Methods: Fourty one HBsAg+ve pregnant women along with 10 healthy controls were enrolled after obtaining informed consent. The HBV DNA in placenta was detected by qPCR using primers for X and core ORF. Expression of NTCP in placenta was analyzed by qRT-PCR and further investigated by immunohistochemistry (IHC) along with HBV replication biomarkers, HBeAg, and HBcAg. Results: HBsAg positive subjects were divided in two groups on the basis of viral load [High Viral Load (HVL) Group; viral load ≥2000IU/ml, Low Viral Load (LVL) Group; viral load <2000IU/ml] according to INASL guidelines 2018. HBV infected females showed increased expression of NTCP in trophoblasts of placenta compared to control group (HVL 3.69,SE 0.13 Vs Control 1.74,SE 0.15, p=0.0117). Furthermore, significant difference in NTCP expression was also observed between HVL and LVL group (HVL 3.69,SE 0.13 Vs LVL 1.98,SE 0.17, p=0.022) and positively correlated with the maternal HBV DNA load. Membranous and/or cytoplasmic immunostaining of NTCP, and cytoplasmic staining of HBeAg and HBcAg in trophoblasts along with presence of HBV DNA indicated that trophoblasts are not only susceptible to HBV infection but may also be a site for viral replication. Conclusions: This is the pioneer study, which demonstrates expression of NTCP on placenta which may facilitate the entry of HBV. Furthermore, the study establishes the presence of HBeAg in placenta of patients without circulating HBeAg, indicating these cells may act as replication host/reservoir. This pioneering finding hints at the possibility of exploring the potential of NTCP blocking strategies in preventing vertical transmission of HBV.

scholarly journals Decreased levels of serum zonulin and copeptin in chronic Hepatitis-B patients

2019 ◽  
Vol 35 (3) ◽  
Author(s):  
Mustafa Kerem Calgin ◽  
Yeliz Cetinkol
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Normal Population ◽  
Antiviral Treatment ◽  
Inverse Correlation ◽  
Systemic Circulation ◽  
Hbv Dna ◽  
Significant Difference

Background & Objective: Liver and intestines are anatomically and physiologically linked. Zonulin is a protein modulating intercellular tight junctions and regulating intestinal permeability. Copeptin was studied as a marker of systemic circulation disorders in research about vasopressin and was associated with liver disease prognosis. Serum zonulin and copeptin levels were measured in patients with diagnosis of chronic hepatitis B (CHB) with the aim of easing antiviral treatment management in clinical applications and to investigate the association with normal population and viral load. Methods: Analysis included the serum of 30 CHB patients and 17 controls. HBV-DNA real-time PCR tests were completed. CHB patients were divided into three subgroups according to viral load in serum. Zonulin and copeptin levels were measured using ELISA kits. Results: Serum zonulin and copeptin levels were significantly low in CHB patients compared to controls (p<0.001). When CHB subgroups are investigated in terms of serum zonulin and copeptin levels, there was an inverse correlation observed with significant difference (p<0.01, p<0.05). Conclusion: The negative correlation between serum zonulin and copeptin with HBV-DNA load revealed in our study shows they may be used to monitor treatment. Zonulin and copeptin assays provide the possibility of developing new approaches to CHB diagnosis and monitoring. doi: https://doi.org/10.12669/pjms.35.3.144 How to cite this:Calgin MK, Cetinkol Y. Decreased levels of serum zonulin and copeptin in chronic Hepatitis-B patients. Pak J Med Sci. 2019;35(3):---------. doi: https://doi.org/10.12669/pjms.35.3.144 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Clinical Features and Resistance to Entecavir Monotherapy of Patients with Hepatitis B

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hideo Takayama ◽  
Takuya Komura ◽  
Takashi Kagaya ◽  
Saiho Sugimoto ◽  
Noriaki Orita ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B ◽  
Clinical Features ◽  
High Viral Load ◽  
Hbv Dna ◽  
Health Concern ◽  
Naive Group ◽  
Rescue Treatment ◽  
Significant Difference ◽  
B Virus

Aim. Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. Methods. A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Results. Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. Conclusions. ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.

scholarly journals Pre-Transplant Donor HBV DNA+ and Male Recipient are Independent Risk Factors for Treatment Failure in HBsAg+ Donors to HBsAg- Kidney Transplant Recipients

2020 ◽  
Author(s):  
Xianding Wang ◽  
Shijian Feng ◽  
Jinpeng Liu ◽  
Turun Song ◽  
Zhongli Huang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Hepatitis B ◽  
Treatment Failure ◽  
Graft Loss ◽  
Significant Risk ◽  
Hbv Dna ◽  
Control Group ◽  
Organ Shortage ◽  
Significant Difference

Abstract Background: In order to lighten the burden of organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on Kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)+ donors to HBsAg- recipients [D(HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity.Methods: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb)+ living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary end-point.Results: 24 donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, however, we did not use any in D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P<0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group became HBV DNA+ or HBsAg+, none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure.Conclusion: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donor with HBV DNA+ and male candidates.

Risk of Hepatitis B Virus (HBV) Reactivation and the Role of Anti-Viral Prophylaxis in Multiple Myeloma Patients with HBV Infection in the Era of Novel Therapies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3882-3882
Author(s):  
Dawn Mya ◽  
Shuting Han ◽  
Yeow Tee Goh ◽  
Daryl Tan
Keyword(s):  
Multiple Myeloma ◽  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
B Virus ◽  
Lamivudine Prophylaxis

Abstract Abstract 3882 Poster Board III-818 Introduction Patients with hepatitis B virus (HBV) infection, defined by the presence of HBV surface antigen (HBsAg), have an increased risk of HBV reactivation when they are on immunosuppressive treatment for multiple myeloma (MM). Although there is no guideline for MM patients with HBV infection, current lymphoma guidelines do recommend that these patients should receive antiviral prophylaxis during and after chemotherapy. Of late, the advent of bortezomib in the management of MM has resulted in a high reported incidence of variecella-zoster reactivation. The risk of HBV reactivation in MM patients with HBV infection undergoing treatment has not been previously studied. As HBV infection is endemic in Asia, we sought to evaluate the prevalence of HBV infection in our patients, the incidence of its reactivation especially in patients receiving bortezomib and the role of anti-viral prophylaxis. Methods Previously untreated MM patients diagnosed from 2000-2008 who were tested for HBsAg in our institution were included. Hepatitis attributable to HBV reactivation was defined as an increase in HBV DNA levels of tenfold, or an absolute increase greater than105 copies/ml in the HBV DNA level. HBV infected patients were prospectively followed. 33% of all patients have been exposed to bortezomib, while 26% received high dose therapy with autologous stem cell transplantation (HDT/ASCT). Results 243 untreated MM patients were identified. The prevalence of HBV infection is 5.8% (14/243). 6 (43%) HBV infected patients had detectable HBV DNA viral load (>3 log) at baseline. All 6 patients had normal baseline liver function tests and received lamivudine prophylaxis. All 14 HBV infected patients went on to receive systemic therapy for MM, with continual monitoring of HBV DNA viral load and liver enzymes for viral reactivation. 4 patients with undetectable HBV DNA load did not receive anti-viral prophylaxis. Of these 14 patients, 3 (21%) who had been on lamivudine prophylaxis had reactivation of the virus, with 1 dying from it, and 1 having emergence of a mutant viral strain. Two of them had no detectable viral load at presentation. Two patients reactivated 3 and 5 months after HDT/ASCT, while 1 reactivated immediately after a bortezomib/ doxil salvage regimen. Conclusion The risk of HBV reactivation appeared to be commonest during the immune reconstitution phase after HDT/ASCT. Although the majority of patients with HBV infection and not receiving HDT/ASCT do not reactivate, the risk may not negligible when bortezomib is used (7%). Undetectable HBV DNA and the use of anti-viral prophylaxis do not appear to preclude reactivation. The optimal use of anti-viral prophylaxis, particularly if bortezomib is given, should be further evaluated. This is particularly relevant in the current era where bortezomib plays a dominant role in the treatment of MM, and especially in endemic regions where the incidence of HBV infection is high. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Study of Correlation between Serum Vitamin D3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1114
Author(s):  
Wang-Sheng Ko ◽  
Yen-Ping Yang ◽  
Fang-Ping Shen ◽  
Mu-Chen Wu ◽  
Chia-Ju Shih ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Vitamin D3 ◽  
Peripheral Blood ◽  
Hepatitis B Surface Antigen ◽  
Serum Vitamin ◽  
Hbv Dna ◽  
Hbv Infection

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20–30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9 ± 5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (β:−6.2, 95% CI: −10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.

scholarly journals Antiviral l-Nucleosides Specific for Hepatitis B Virus Infection

2001 ◽  
Vol 45 (1) ◽  
pp. 229-235 ◽  
Author(s):  
Martin L. Bryant ◽  
Edward G. Bridges ◽  
Laurent Placidi ◽  
Abdesslem Faraj ◽  
Anna-Giulia Loi ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Virus ◽  
Hbv Infection ◽  
Virus Surface ◽  
Chronic Hbv Infection ◽  
Hbv Replication ◽  
B Virus ◽  
Chronic Hbv

ABSTRACT A unique series of simple “unnatural” nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3′-OH group of the β-l-2′-deoxyribose of the β-l-2′-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides β-l-2′-deoxycytidine, β-l-thymidine, and β-l-2′-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (α, β, and γ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

scholarly journals Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with Standard Chemoimmunotherapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4235-4235
Author(s):  
Chieh-Lung Cheng ◽  
Erin Huang ◽  
Ming-Kai Chuang ◽  
Wen-Chien Chou ◽  
Hwei-Fang Tien
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
Hepatitis B Surface Antigen ◽  
B Cell Lymphoma ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hbsag Positivity ◽  
Large B Cell Lymphoma ◽  
Significant Difference

Abstract Introduction Hepatitis B virus (HBV) is one of the most common viral infections in humans. Global prevalence of chronic HBV infection is heterogeneous, with 2-20% of a given population being infected with HBV. In some parts of Africa, Asia and South America, HBV infection is endemic and remains to be a significant public health issue.Previous studies have shown a positive association between hepatitis B surface antigen (HBsAg)-positive HBV infection and B-cell non-Hodgkin lymphoma (NHL), such as diffuse large B-cell lymphoma (DLBCL), the most common subtype of B-cell NHL. Nevertheless, the clinical characteristics of HBsAg positivity and negativity, as well as their prognostic implications in DLBCL patients treated with frontline standard chemoimmunotherapy remain to be clarified. Methods We conducted a single-institution retrospective study in a tertiary referral hospital in Taiwan, an HBV prevalent country in Asia. From January 2001 to December 2015, patients aged ≥20 years with newly diagnosed DLBCL treated with standard rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were selected. Retrospective chart review was performed to collect data on clinical features, laboratory profiles, serum markers for HBV infection such as HBsAg and HBV-DNA loads before chemotherapy, as well as data on treatment response and outcome. The cohort was followed up until the cutoff date of June 30, 2018. Results A total of 393 DLBCL patients were analyzed in this study, with a median age of 60.5 years (range, 23.5 years to 90.9 years) and the sex ratio of 1.38 to 1.The 5-year overall survival (OS) rates were 65.2% after a median follow-up time of 68.8 months. In this cohort, 100 patients (25.4%) were found to have HBsAg positivity before treatment.Eighty-two of them had received prophylactic antiviral therapy, including 28 with lamivudine, 44 with entecavir and 10 with others. Besides, forty-five of HBsAg-positive patients had data of serum HBV-DNA loads before treatment, and 44 of them had received prophylactic anti-HBV therapy. Compared to HBsAg-negative patients, HBsAg-positive patients had a younger median onset age (55.9 years vs. 61.4 years, P=0.004), a trend of more advanced stage (stage III/IV: 62% vs. 51.2%, P=0.064), higher serum LDH levels at diagnosis (62% vs. 50.2%, P=0.048), and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (high-intermediate/high: 50% vs. 41.6%, P=0.162). Regarding to treatment response and outcome, HBsAg-positive patients, compared to HBsAg-negative patients, had a trend of lower overall response rates (78% vs. 84.3%, P=0.169) and complete remission rates (73% vs. 79.9%, P=0.163). Furthermore, compared to HBsAg-negative patients, HBsAg-positive patientshad a poorer median OS (median OS, not reached vs. 95.8 months, P=0.001, Figure 1) and a shorter median progression-free survival (PFS) (median PFS, not reached vs. 34.3 months, P=0.031), respectively. By multivariate analysis, HBsAg positivity is an independent poor prognostic factor for OS irrespective of NCCN-IPI score, serum albumin levels and B symptoms. No significant difference was found in outcome between patients with high HBV-DNA loads (> 2000 IU/mL, n=21) and those with low HBV-DNA loads (≤2000 IU/mL, n=24). With respect to prophylactic anti-HBV treatment, patients without prophylactic therapy (n=18), compared to those with prophylactic therapy (n=82), had a trend of shorter median OS (27.9 months vs. 96.2 months, P=0.346). Moreover, no significant difference was found in median OS between HBsAg-positive patients when administrated with anti-HBV lamivudine and those when administrated with anti-HBV entecavir. Conclusions This study demonstrated that HBsAg positivity has unique clinical relevance to patients with DLBCL, as well as its impact in the efficacy of treatment. HBsAg positivity may serve as a relevant biomarker to predict clinical outcome in DLBCL patients treated with R-CHOP. Prophylactic anti-HBV therapy may be of great importance in HBsAg-positive DLBCL patients. Further studies to explore the etiopathogenesis of HBV infection in DLBCL may help to discovery new treatment targets to improve the outcome of this group of patients. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals The cooperative complex of Argonaute-2/MicroRNA-146a regulates Hepatitis B Virus replication through FEN1

2020 ◽  
Author(s):  
min ji ◽  
Xiaoping Mei ◽  
Xunming Jing ◽  
Xu Xu ◽  
Xing Chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Expression Level ◽  
Control Group ◽  
Transcriptional Level ◽  
Downstream Target ◽  
Hbv Replication ◽  
Hbv Cccdna ◽  
B Virus

Abstract Background: The regulatory of HBV replication is still unclear. FEN1 can repair HBV rcDNA to HBV cccDNA and promote HBV DNA replication. However, its specific regulatory detail remains unclear. MicroRNA regulates gene expression at post-transcriptional level. Especially, miR-146a, it plays an important role that is closely related to regulation of HBV replication. Based on above, we hypothesize that miR-146a may be regulate HBV cccDNA formation through FEN1. So, we will investigate the effect of miR-146a on the replication of hepatitis B virus and its molecular mechanism. Results: We found that level of miR-146a was significantly up-regulated in HepG2.2.15 cells (11.755±0.069) than that in HepG2 (1.000±0.038) (P<0.05). Furthermore, HBV-DNA copies and FEN1 were significantly increased and decreased, respectively, in HepG2.2.15 cells transfected with miR-146a mimic and inhibitor for 48h,[(3.215±0.001); (2.623±0.083)] compared with the control group (2.813±0.015) (P<0.05),. After transfection FEN1 plasmid, HBV-DNA Copies (5.712±0.371) is significantly higher than the control group（2.661±0.009）(P<0.05), and the level of miR-146a（3.431±0.004）is significantly higher than the control group (1.023±0.224） (P<0.05). The expression level of IRAK1/TRAF6 are significantly lower and higher [(0.114±0.013); (0.390±0.014); (1.222±0.073); (2.145±0.271)] than the control group [(1.000±0.038); (1.007±0.119)] (P<0.05) after transfection miR-146a mimic and inhibitor into HepG2.2.15. After Ago2 siRNA, the level of miR-146a (0.105±0.002) is significantly decreased than the control group (1.000±0.041) (P<0.05) from Ago2 protein RIP. After transfection Ago2 siRNA then added into exogenous miR-146a into HepG2.2.15, The expression level of FEN1 is significantly reduced (0.485±0.100) than the control group (1.000±0.023) (P<0.05), and the HBV-DNA copies is significantly lower (3.230±0.047) than the control group (3.789±0.041) (P<0.05). Conclusion: Ago2 cooperates with miR-146a to regulate the transcription the expression level of FEN1 protein through the downstream target gene IRAK1/TRAF6, then promoting HBV replication.

scholarly journals MicroRNA miR-212-3p targets NFIA to suppress HBV replication and tumor progression in hepatocellular carcinoma via repressing Enhancer I activity

2021 ◽  
Author(s):  
Hui Tian ◽  
Zhenkun He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Cell Viability ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Hbv Replication ◽  
Dual Luciferase Reporter Assay

IntroductionEmerging evidence identifies that microRNAs (miRNAs) are associated with hepatitis B virus (HBV) infection. In the current study, we mainly focus on the functions and underlying mechanisms of miR-212-3p in HBV replication in hepatocellular carcinoma (HCC).Material and methodsThe levels of miR-212-3p, nuclear factor I A (NFIA) and HBV DNA copies were measured by qRT-PCR. The level of core particle-associated HBV DNA, the productions of hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg), and the expression of NFIA were detected via southern blot assay, ELISA and western blot assay, respectively. The putative target of miR-212-3p was predicted by TargetScan and Pictar, followed by the dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay to validate the interaction. The interaction between miR-212-3p and Enhancer I/X promoter (EnI/Xp) reporter was also verified by dual luciferase reporter assay. In addition, the cell viability and apoptotic rate were detected by MTT and flow cytometry, respectively.ResultsmiR-212-3p mimics or NFIA knockdown inhibited HBV expression and replication in HepG2.2.15 cells, while miR-212-3p inhibitor or NFIA overexpression showed the opposite trend. NFIA was confirmed as a direct target of miR-212-3p. Furthermore, miR-212-3p impeded HBV expression and replication by suppressing NFIA. Besides, miR-212-3p lowered EnI/Xp activity by regulating NFIA. In addition, miR-212-3p retarded cell viability and induced apoptosis through targeting NFIA.ConclusionsmiR-212-3p targets NFIA to down-regulate its expression, thereby inhibiting HBV replication and tumorigenesis in HCC. Our finding might provide a promising therapeutic target for HBV infection.

scholarly journals Comparison of Anti-Hepatitis B Virus Activities of Lamivudine and Clevudine by a Quantitative Assay

2003 ◽  
Vol 47 (1) ◽  
pp. 324-336 ◽  
Author(s):  
Ayman M. Abdelhamed ◽  
Colleen M. Kelley ◽  
Thomas G. Miller ◽  
Phillip A. Furman ◽  
Edward E. Cable ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Treatment ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Extracellular Dna ◽  
Quantitative Assay ◽  
Hbv Replication ◽  
B Virus

ABSTRACT In this study, we used a quantitative assay to measure the concentration-dependent effects of antivirals on extracellular hepatitis B virus (HBV) DNA as well as on different cytoplasmic and nuclear forms of HBV DNA that participate in HBV replication. HBV recombinant baculovirus, which efficiently delivers the HBV genome to HepG2 cells, was used for this study because (i) antivirals can be administered prior to initiation of HBV infection or after HBV infection and (ii) sufficiently high HBV replication levels are achieved that HBV covalently closed circular (CCC) DNA can be easily detected and individual HBV DNA species can be quantitatively analyzed separately from total HBV DNA. The results showed that the levels of HBV replicative intermediate and extracellular DNA decreased in a concentration-dependent fashion following antiviral treatment. The 50% effective concentration (EC50) and EC90 values and the Hill slopes differed for the different HBV DNA species analyzed. The data clearly indicated that (i) nuclear HBV DNAs are more resistant to antiviral therapy than cytoplasmic or extracellular HBV DNAs and (ii) nuclear HBV CCC DNA is more resistant than the nuclear relaxed circular form. This report presents the first in vitro comparison of the effects of two antivirals administered prior to initiation of HBV infection and the first thorough in vitro quantitative study of concentration-dependent antiviral effects on HBV CCC DNA.

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