scholarly journals Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 757
Author(s):  
João Diogo Dias ◽  
Nazim Sarica ◽  
Christine Neuveut

Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments efficiently control virus replication and improve liver function, they cannot cure HBV infection. Viral persistence is due to the maintenance of the viral circular episomal DNA, called covalently closed circular DNA (cccDNA), in the nuclei of infected cells. cccDNA not only resists antiviral therapies, but also escapes innate antiviral surveillance. This viral DNA intermediate plays a central role in HBV replication, as cccDNA is the template for the transcription of all viral RNAs, including pregenomic RNA (pgRNA), which in turn feeds the formation of cccDNA through a step of reverse transcription. The establishment and/or expression of cccDNA is thus a prime target for the eradication of HBV. In this review, we provide an update on the current knowledge on the initial steps of HBV infection, from the nuclear import of the nucleocapsid to the formation of the cccDNA.

2014 ◽  
Vol 39 (2) ◽  
pp. 65-68 ◽  
Author(s):  
K Fatema ◽  
S Tabassum ◽  
A Nessa ◽  
M Jahan

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


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Gideon K. Helegbe ◽  
Faiza Tanko ◽  
Paul A. Aryee ◽  
Setor Aku Lotsu ◽  
Mathias J. A. Asaarik ◽  
...  

The Bolgatanga Municipal Health Directorate has reported liver cirrhosis among the first three diseases causing mortality from 2013 to 2015. This implicates hepatitis B virus (HBV) infection considering its high prevalence among blood donors in the Upper East Region of Ghana. However, for a vulnerable group such as market women, there is not much information with regard to the prevalence, knowledge, and attitude towards HBV infection. Thus, this study sought to bridge this gap by determining the seroprevalence, knowledge, and attitude of market women in the Bolgatanga Municipality of Ghana, towards HBV infection. A cross-sectional descriptive study was conducted (from October 2017 to March 2018) among 404 market women using a pretested questionnaire to ascertain the knowledge and attitudes of market women towards HBV infection, while hepatitis B surface Antigen Rapid Diagnostic Test strips were used to screen for the infection. The study revealed that the seroprevalence of hepatitis B among the market women was 15.6%, and majority of the study subjects (>60%) were unaware of HBV infection. Overall, knowledge on and attitude towards HBV infection were low and poor, respectively, with a significantly high number of the market women not wanting infected individuals to be isolated (p=0.049). A high seroprevalence, together with poor attitude and low knowledge levels, as seen in this study is of great public health concern. The study recommends regular HBV screening for market women for prompt treatment and vaccination as well as continuous health education to increase knowledge level and improve the poor attitudes of market women towards HBV infection.


Gut ◽  
2012 ◽  
Vol 61 (Suppl 1) ◽  
pp. i6-i17 ◽  
Author(s):  
Maura Dandri ◽  
Stephen Locarnini

Chronic hepatitis B virus (HBV) infection remains a major health burden and the main risk factor for the development of hepatocellular carcinoma worldwide. However, HBV is not directly cytopathic and liver injury appears to be mostly caused by repeated attempts of the host's immune responses to control the infection. Recent studies have shown that the unique replication strategy adopted by HBV enables it to survive within the infected hepatocyte while complex virus–host interplays ensure the virus is able to fulfil its replication requirements yet is still able to evade important host antiviral innate immune responses. Clearer understanding of the host and viral mechanisms affecting HBV replication and persistence is necessary to design more effective therapeutic strategies aimed at improving the management of patients with chronic HBV infection to eventually achieve viral eradication. This article focuses on summarising the current knowledge of factors influencing the course of HBV infection, giving emphasis on the use of novel assays and quantitative serological and intrahepatic biomarkers as tools for predicting treatment response and disease progression.


Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1691
Author(s):  
Eriko Ohsaki ◽  
Yadarat Suwanmanee ◽  
Keiji Ueda

Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating covalently closed circular (ccc) DNA. More recently, therapeutic strategies targeting various stages of the HBV lifecycle have been attempted. Although cccDNA-targeted therapies are attractive, there are still many problems to be overcome, and the development of novel polymerase inhibitors remains an important issue. Interferons and nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are the only therapeutic options currently available for HBV infection. Many studies have reported that the combination of interferons and NRTI causes the loss of hepatitis B surface antigen (HBsAg), which is suggestive of seroconversion. Although NRTIs do not directly target cccDNA, they can strongly reduce the serum viral DNA load and could suppress the recycling step of cccDNA formation, improve liver fibrosis/cirrhosis, and reduce the risk of hepatocellular carcinoma. Here, we review recent studies on combination therapies using polymerase inhibitors and discuss the future directions of therapeutic strategies for HBV infection.


Author(s):  
Irene Jose Manjiyil ◽  
Kavitha Paul Konikkara

Introduction: Hepatitis B Virus (HBV) infection remains a significant global health concern that may cause acute or chronic hepatitis. Chronically infected patients are at risk for cirrhosis and hepatocellular carcinoma. The disease causes a problem in the tribal communities. There are lack of studies on the prevalence of HBV among the tribal population. Aim: To assess the seroprevalence of HBV infection among the tribal population of Attapady, Kerala. Materials and Methods: This was a community based cross- sectional study conducted on serum samples collected from 269 subjects among the tribal population of Attapady. Serum samples were tested for quantitative antibody to HBsAg (anti-HBs), Hepatitis B surface antigen (HBsAg) and Hepatitis B envelope antigen (HBeAg) Enzyme Linked Immunosorbent Assay (ELISA). Total hepatitis B core antibody (anti-HBc) and IgM antibody to hepatitis B core antigen (anti HBc IgM), frequencies were obtained using proportion and 95% Confidence Interval CI. Results: The seroprevalence of HBsAg was 10.4%. HBeAg was detected in 7.1% of HBsAg positive patients. 21.2% had protective anti-HBs titer. Anti-HBe was detected in five patients. Anti-HBc total and anti-HBc IgM were positive for 26.7% and 2.6%, respectively. Anti-HBc IgM alone and isolated anti-HBc were detected in 1.5% and 5.9 %, respectively. Anti-HBs and anti-HBc total both became positive in 8.6% cases. Conclusion: HBV infection poses a huge burden on tribal health. All HBsAg positive patients should be tested further to determine the stage of the disease. There is need to explore high HBV prevalence areas with studies on associated risk factors to bring out the ongoing transmission process and focus on preventive measures. HBV vaccination, antenatal screening, and health awareness should be given priority to tackle the burden.


2021 ◽  
Vol 22 (11) ◽  
pp. 5497
Author(s):  
Arshi Khanam ◽  
Joel V. Chua ◽  
Shyam Kottilil

More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination. In chronic HBV infection, significant alterations in both innate and adaptive immunity including expansion of regulatory cells, overexpression of co-inhibitory receptors, presence of abundant inflammatory mediators, and modifications in immune cell derived exosome release and function occurs, which overpower antiviral response leading to persistent viral infection and subsequent immune pathologies associated with disease progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, we discuss the current knowledge of innate and adaptive immune cells transformations that are associated with immunopathogenesis and disease outcome in CHB patients.


2019 ◽  
Vol 7 (3) ◽  
pp. 435-439
Author(s):  
Osama Al Wutayd ◽  
Abdullah AlRehaili ◽  
Khaled AlSafrani AlSafrani ◽  
Abdulrahman Abalkhail ◽  
Sulaiman Mohammed AlEidi

BACKGROUND: Medical students are exposed to occupational health hazards in hospitals during their studies and lack sufficient education about infection control measures. Injury to medical students is a substantial problem and students have an increased risk of hepatitis B virus (HBV). To understand how medical students think about infection control, it is important to identify the strengths and weaknesses of their education. AIM: To assess current knowledge, attitudes, and practice of medical students regarding HBV infection and control measures at Qassim University, Saudi Arabia. MATERIAL AND METHODS: A cross-sectional study was conducted at a medical college. Participants completed a 39-item self-administered questionnaire assessing demographics, knowledge, attitudes, and practice. Item response frequencies were calculated. Responses were recorded into yes (strongly agree and agree) and no (neutral, disagree, and strongly disagree) answers. Correct responses were totalled and categorised as good or poor performance. A scale cut-off of less than 75% correct responses was considered poor, and 75% or more correct responses was considered good. Odds ratios and 95% confidence intervals were calculated, and the chi-square test was used for analysis. RESULTS: A total of 21%, 41%, and 8% of students expressed good knowledge, attitudes, and practice, respectively. There was no statistically significant difference between males and females on knowledge (p = 0.089), attitudes (p = 0.829), and practice (p = 0.248). There was a statistically significant difference between academic years on knowledge (p = 0.0001), attitudes (p = 0.0001), and practice (p = 0.0001). CONCLUSION: Most medical students have poor knowledge, attitudes, and practice regarding the risk of HBV infection. It is recommended that a policy is implemented for training on infection prevention for all medical students before they start clinical practice. Prevention programs about HBV infection should be instituted, and existing programs must be strengthened.


2011 ◽  
Vol 6 (04) ◽  
pp. 340-346 ◽  
Author(s):  
Olfat Shaker ◽  
Amal Ahmed ◽  
Inas Abdel Satar ◽  
Hamza El Ahl ◽  
Wafaa Shousha ◽  
...  

Introduction: Thalassemia is hereditary anemia which requires lifelong transfusion as treatment, and hepatitis viral infection is one of the risks of repeated transfusions. Hepatitis B outbreaks in health-care settings are still a serious public health concern worldwide. Blood samples negative for HBsAg but positive for HBV-DNA, with or without the presence of HBV antibodies, are classified as "occult" HBV infection (OBI). This study investigated the prevalence of occult HBV infection in Egyptian thalassemic children. Methodology:  Eighty patients admitted to the Faculty of Medicine, Cairo University Hospital, were involved in this prospective study. Strict inclusion criteria were set to nullify the effect of confounding variables and further minimize selection bias. The following laboratory investigations were performed: complete blood count (CBC); serum AST and ALT; albumin; bilirubin; HBsAg; HBeAg; HBcAb; HCV-RNA; and HBV-DNA. Results: All our patients had no clinical manifestation suggestive of hepatitis. Molecular biology studies revealed positivity for HCV and HBV at 25% and 32.5% respectively. Conclusion: The estimated risk of acquiring hepatitis B and C infection in children receiving multiple blood transfusions is surprisingly high. Moreover, occult hepatitis B infection is a considerably risk.


2021 ◽  
Author(s):  
Yan Yan ◽  
Chantsalmaa Davgadorj

The use of replication-competent hepatitis B virus (HBV) DNA to construct a mouse model will help explore antiviral treatment strategies for more than 240 million patients infected with HBV worldwide. Eradication of chronic HBV infection can effectively block the adverse consequences of HBV-induced hepatic cirrhosis, failure and carcinoma. The core reason that HBV is difficult to eradicate is that most of infected people develop chronic HBV infection due to the establishment of immune tolerance. Here, we introduce a mouse model of adeno-associated virus (AAV)-HBV transfection, which produces HBV surface antigen (HBsAg) that can be maintained for more than 6 months. During virus replication, intermediates, transcripts, and proteins can be detected in peripheral blood. At the same time, the prerequisite for studying liver disease formation and immunotherapy through in vitro experiments is to isolate hepatic subgroup cells. Here, we describe a cell sorting method based on liberase perfusion technology combined with low-speed centrifugation and magnetic bead antibody labeling to purify hepatic parenchymal cells (PCs) and non-parenchymal cells (NPCs) step by step from murine liver, such as hepatic sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), which will help accelerate the study of the genetic and clearance mechanistic of chronic HBV infection.


Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 63 ◽  
Author(s):  
Duaa W. Al-Sadeq ◽  
Sara A. Taleb ◽  
Roan E. Zaied ◽  
Sara M. Fahad ◽  
Maria K. Smatti ◽  
...  

Hepatitis B virus (HBV) is an enveloped partial double-stranded DNA virus that can cause acute and chronic hepatitis. According to the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), 257 million people are living with HBV. Moreover, 20,900 acute hepatitis B cases were reported in 2016. Hepatitis B is highly prevalent in the African, Western Pacific, Eastern Mediterranean, South-East Asia, and European regions, respectively. Due to the high mutational rate of HBV and lack of reverse transcriptase proofreading activity, ten different genotypes with different geographical distributions have been identified. HBV pathogenesis and severity of infection depend on several host and viral factors, particularly, the genetic variability of both the host and virus. Although HBV infection is a global health concern, there is a lack of adequate studies and reports in the Middle East and North Africa (MENA) region. Here, we provide a review on HBV epidemiology, pathogenesis, host–pathogen interactions, coinfection with selected viruses, and laboratory diagnosis, focusing on studies conducted in the MENA region to determine the current situation of the HBV infection and outline the future study areas.


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