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Introduction
Professor Anna Kramvis is a Research Professor and Director of the Hepatitis Virus Diversity Research Unit (HVDRU), University of the Witwatersrand, Johannesburg, South Africa. The HVDRU (www.wits.ac.za/health/hvdru) provides a platform for training of research scientists in molecular virology. Her primary research interest is the molecular virology of the hepatitis B virus (HBV) and hepatitis C virus (HCV), especially of uniquely African strains, which differ from those found in other regions of the world. No infectious diseases research in Africa can neglect the AIDS pandemic scourging our continent, so, in addition to HBV-mono-infection, her team is researching HBV/HIV co-infection and developing bioinformatics tools to facilitate the study of these infections.
Current institution
Publications
Publications (437)
Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solid tumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy, only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations. MicroRNAs (miRNAs) act...
HBeAg is a non-structural, secreted protein of hepatitis B virus (HBV). Its p25 precursor is post-translationally modified in the endoplasmic reticulum. The G1862T precore mutation leads to the accumulation of P25 in the endoplasmic reticulum and activation of unfolded protein response. Using mass spectrometry, comparative proteome profiling of Huh...
In sub-Saharan Africa (SSA), the (sub)genotypes A1, D3, and E of the hepatitis B virus (HBV) prevail. Individuals infected with subgenotype A1 have a 4.5-fold increased risk of HCC compared to those infected with other (sub)genotypes. The effect of (sub)genotypes on protein expression and host signalling has not been studied. Mass spectrometry was...
Aim
This study aimed to determine the kinetics of occult hepatitis B virus infections (OBI) among people with HIV (PWH).
Methods
The study used archived plasma samples from longitudinal HIV natural history studies. We identified new OBI cases and assessed risk factors for OBI using Cox proportional hazards regression analysis.
Results
At baseline...
Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps re...
Aim: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) particularly in African populations, in whom malignancy frequently presents at an advanced stage with poor outcomes. We derived HBV whole genome sequences (WGS) from individuals with HCC and compared them to sequences from individuals without HC...
The present review article presents the key messages of the 8th Workshop on Paediatric Virology organised virtually by the Institute of Paediatric Virology based on the island of Euboea in Greece. The major topics covered during the workshop were the following: i) New advances in antiviral agents and vaccines against cytomegalovirus; ii) hantavirus...
Vaccination against hepatitis B virus (HBV) remains the most effective strategy against HBV infection in humans. The present review summarized the optimal vaccination strategies against HBV in childhood. The following points are discussed: i) When and how the first HBV vaccines were developed; ii) the dosages, schedules and injection routes that ar...
Background:
Hepatitis B virus (HBV) infection causes nearly 300 million chronic infections globally. Healthcare workers face up to four times the risk of HBV infection through occupational exposure to contaminated blood and bodily fluids. Health sciences students (HSSs) are regarded as at an even greater risk as they embark on their clinical train...
Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is associated with the pathogenesis of hepatocellular carcinoma, and various HBV proteins have been imp...
Background: Health-care students (HCSs) are at risk of occupational exposure to hepatitis B virus (HBV) infection despite an effective hepatitis B vaccine (HepB) being available. The majority of current HCSs are born after HepB was introduced into the South African Expanded Programme on Immunisation in 1995. Thus, it is assumed that having received...
Background
Hepatitis C virus (HCV) is a global public health problem, with ~ 11 million people in Africa infected. There is incomplete information on HCV in Sudan, particularly in haemodialysis patients, who have a higher prevalence compared to the general population. Thus, our objectives were to genotype and molecularly characterize HCV isolated f...
Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype A1. The virus remains a significant burden on public health in SA d...
The world has seen the emergence of a new virus in 2019, SARS-CoV-2, causing the COVID-19 pandemic and millions of deaths worldwide. Microscopy can be much more informative than conventional detection methods such as RT-PCR. This review aims to present the up-to-date microscopy observations in patients, the in vitro studies of the virus and viral p...
Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies....
Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35–57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 e...
The present article provides an overview of the key messages of the topics discussed at the '7th Workshop on Paediatric Virology', which was organised virtually on December 20, 2021 by the Institute of Paediatric Virology, located on the Island of Euboea in Greece. The workshop's plenary lectures were on: i) viral pandemics and epidemics in the anc...
Despite the early promise of RNA therapeutics as a magic bullet to modulate aberrant signaling in cancer, this field remains a work-in-progress. Nevertheless, RNA therapeutics is now a reality for the treatment of viral diseases (COVID-19) and offers great promise for cancer. This review paper specifically investigates RNAi as a therapeutic option...
Background
Tenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported.
Case presentation
Here we describe a case of a 5-year old, asympto...
Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge s...
The paucity of animal models that simulate the replication of the hepatitis B virus (HBV) is an impediment to advancing new anti-viral treatments. The work reported here employed recombinant adeno-associated viruses (AAVs) to model HBV subgenotype A1 and subgenotype D3 replication in vitro and in vivo. Infection with subgenotype A1 is endemic to pa...
With the highest annual fatality ratio (mortality-to-incidence ratio), reported for a human cancer, hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide and its distribution is not uniform. In Sub-Saharan Africa (SSA), HCC is the second leading cause of cancer-related deaths for men and the fourth for w...
Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus that belongs to the family Flaviviridae. HCV is characterized by extensive genetic heterogeneity and has been classified into genotypes, subtypes and recombinant forms (RFs). Revised HCV classification, based on phylogenetic analysis of a large number of nearly full-length sequen...
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) pathogenesis is fueled by persistent HBV infection that stealthily maintains a delicate balance between viral replication and evasion of the host immune system. HBV is remarkably adept at using a combination of both its own, as well as host machinery to ensure its own replication...
HBeAg, a non-particulate protein of hepatitis B virus (HBV), is translated from the precore/core region as a precursor, which is post-translationally modified. Subgenotype A1 of HBV, which is a risk factor for hepatocellular carcinoma (HCC), has unique molecular characteristics in the basic core promoter/precore regions. Carriers of A1 exhibit earl...
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. T...
Description of the spatial characteristics of viral dispersal is important in understanding the history of infections. Nine hepatitis B virus (HBV) genotypes (A-I), and a putative 10th genotype (J), with distinct geographical distribution, are recognized. In sub-Saharan Africa (sub)-genotypes A1, D3 and E circulate, with E predominating in western...
In South Africa (SA), hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma (HCC). As HBV genotypes/subgenotypes and mutations can influence disease manifestation and progression, our aim was to molecularly characterize HBV in Black cancer patients, with and without HCC. The basal core promoter/precore (BCP/PC) and...
Currently, the treatment of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) [HBV-HCC] relies on blunt tools that are unable to offer effective therapy for later stage pathogenesis. The potential of miRNA to treat HBV-HCC offer a more targeted approach to managing this lethal carcinoma; however, the complexity of miRNA as an ancill...
Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major c...
Purpose of review:
The aim of this article is to highlight the unique challenges for hepatitis B virus (HBV) cure faced in resource-limited settings (RLS) in sub-Saharan Africa (SSA), where access to disease prevention measures, medical testing, and treatment are limited.
Recent findings:
SSA RLS face challenges, which need to be anticipated as...
The nomenclature of the hepatitis B virus (HBV) genes and their products has developed stepwise, occasionally in an erratic way, creating many misunderstandings, especially among those who do not know the structure of HBV and its genome in detail. One of the most frequent misunderstandings, even presented in leading journals, is the designation of...
The incidence and mortality of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) is an intractable public health problem in developing countries that is compounded by limited early detection and therapeutic options. Despite the early promise of utilizing the regulatory role of miRNA in liver cancer, this field remains largely in...
Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists f...
The hepatitis B virus (HBV) genome has ∼3 200 nucleotides, coding for seven proteins in four overlapping open reading frames (ORFs). Comparison of genomic coordinates between different samples and/or published literature requires manual conversion. An online tool is presented to convert nucleotide or amino acid positions between ORFs, regions and d...
The hepatitis B virus (HBV) genome has ∼3 200 nucleotides, coding for seven proteins in four overlapping open reading frames (ORFs). Comparison of genomic coordinates between different samples and/or published literature requires manual conversion. An online tool is presented to convert nucleotide or amino acid positions between ORFs, regions and d...
Both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection are highly endemic in sub‐Saharan Africa. This study examined serological and clinical follow‐up data from 39 HBV‐positive, HIV‐positive black South African adults, who returned for follow‐up at 3, 6, 12 and 18 months post‐initiation of anti‐retroviral therapy (ART). Of t...
Hepatitis B virus (HBV) infection, a global public health problem can be asymptomatic, acute or chronic and can lead to serious consequences of infection, including cirrhosis, and hepatocellular carcinoma. HBV, a partially double stranded DNA virus, belongs to the family Hepadnaviridae, and replicates via reverse transcription of an RNA intermediat...
The biosocial background in which the hepatitis B virus (HBV) carrier state with membranous nephropathy (MN) develops was studied by evaluating HBV carriage and proteinuria among 195 family members and household contacts of 31 index HBV carrier children with MN. Unrelated individuals from the communities of these index cases who were negative for H...
The World Health Organization plans to eliminate hepatitis B and C Infections by 2030. Therefore, there is a need to study and understand hepatitis B virus (HBV) epidemiology and viral evolution further, including evaluating occult (HBsAg-negative) HBV infection (OBI), given that such infections are frequently undiagnosed and rarely treated. We aim...
Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in silico approaches, which predict the effect of amino...
32 33 Hepatitis B virus (HBV) infection constitutes a global public health problem. 34 In order to establish how HBV was disseminated across different geographic regions, 35 we estimated the levels of regional clustering for genotypes D and A. We used 916 36 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. 37 Phyloge...
Hepatitis B virus (HBV), a DNA virus, replicates via an RNA intermediate, through reverse transcription catalysed by the viral polymerase that lacks proof reading ability. Thus sequence heterogeneity is a feature of HBV being classified into at least 9 genotypes and over 35 subgenotypes. Africa has a high diversity of genotypes/subgenotypes, with d...
Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis...
Background:
In South Africa (SA), liver cancer (LC) is a public health problem and information is limited.
Methods:
Joinpoint regression analysis was computed for the most recent LC mortality data from Statistics South Africa (StatsSA), by age group, sex and population group. The mortality-to-incidence ratios (MIRs) were calculated as the age-ad...
List of papers for HBV genotype D sequences included in the analysis.
List of papers for HBV genotype A sequences included in the analysis.
List of countries within each geographic region (as defined by the Global Burden of Disease classification system), in which HBV genotype D sequences were included in the analysis.
Sampling and percentages of clustering of HBV genotype D sequences from different countries and geographic regions.
Sampling and percentages of clustering of HBV genotype A sequences from different countries and geographic regions.
List of countries within each geographic region (as defined by the Global Burden of Disease classification system), in which HBV genotype A sequences were included in the analysis.
More than 250 million people worldwide are chronically infected with the hepatitis B virus (HBV). In this Comment, members of the International Coalition to Eliminate HBV appraise the current policy environment and the need for appropriate cure research and preparedness to complement the WHO global elimination strategy, the HBV vaccine and the well...
Objective
The aims of this study were to determine the prevalence of risk factors associated with hepatocellular carcinoma (HCC) in black adult South Africans and to estimate the size of the associated risks.
Methods
A case-control analysis of 150 black South African patients (aged 18–75 years) with HCC—who were a subset of patients recruited for...
Background: Drug users act as reservoirs and transmission channels for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections to the general population worldwide. Periodic epidemiological studies to monitor the prevalence and genetic diversity of these infections to inform on interventions are limited.
O...
The 3rd Workshop on Paediatric Virology, which took place on October 7th, 2017 in Athens, Greece, highlighted the role of breast feeding in the prevention of viral infections during the first years of life. Moreover, it focused on the long-term outcomes of respiratory syncytial virus and rhinovirus infections in prematurely born infants and emphasi...
The G1862T mutation, which occurs most frequently in subgenotype A1 of the hepatitis B virus (HBV), results in a valine to phenylalanine substitution at the 3 position of the signal peptide cleavage site at the amino end of the precore/core (preC/C) precursor protein. The objective of this study was to functionally characterize the G1862T mutation...
Objectives:
Molecular characteristics of hepatitis B virus (HBV), such as genotype and genomic mutations, may contribute to liver-related morbidity and mortality. The association of these characteristics with liver fibrosis severity in sub-Saharan Africa is uncertain. We aimed to characterize molecular HBV features in HIV/HBV co-infected Nigerians...
In the era of combination therapy for human immunodeficiency virus (HIV), liver disease including hepatocellular carcinoma (HCC), are the major causes of death for patients co-infected with hepatitis B virus (HBV) and HIV. However, the mechanisms remain obscure. We aimed to determine whether HCC-related HBV mutations including 1762T/1764A double mu...
Abstract. The ‘2nd Workshop on Paediatric Virology’, which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV‑1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for...
Background
Hepatitis B virus (HBV) DNA sequence data from thousands of samples are present in the public sequence databases. No publicly available, up-to-date, multiple sequence alignments, containing full-length and subgenomic fragments per genotype, are available. Such alignments are useful in many analysis applications, including data-mining and...
Background:
Hepatitis B virus (HBV) is hyperendemic in southern Africa, with subgenotype A1 prevailing. The precore/core (preC/C) region of A1, encoding for hepatitis B e antigen (HBeAg), has unique sequence characteristics, differentiating it from subgenotypes A2 and D3. Our aim was to follow the expression of HBeAg in vitro by the three subgenot...
Although a successful vaccine against HBV has been implemented in 184 countries, eradication of hepatitis B virus (HBV) is still not on the horizon. There are over 240 million chronic carriers of HBV globally. The risk of developing chronic hepatitis ranges from >90% in newborns of hepatitis Be antigen (HBeAg)-positive mothers, 25%-35% in children...
Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence‑based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of...
DNA sequence analysis is undertaken in many biological research laboratories. The workflow consists of several steps involving the bioinformatic processing of biological data. We have developed a suite of web-based online bioinformatic tools to assist with processing, analysis and curation of DNA sequence data. Most of these tools are genome-agnost...
Human immunodeficiency virus (HIV) infection in Sub-Saharan Africa is complicated by co-infection with hepatitis B and C viruses (HBV and HCV), which share similar transmission routes. The aims of this study were to determine the prevalence of hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative HBV infection and of HCV infection among H...
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common routes of blood-borne transmission. In HBV mono-infected Sudanese individuals, genotypes D, E, and A circulate. The objective of this study was to molecularly characterize HBV from HBV/HIV co-infected individuals.
The polymerase overlapping the S region and the basic core p...
Brazil is a country of low hepatitis B virus (HBV) endemicity in which the genotype A of HBV (HBV/A) is the most prevalent. The complete nucleotide sequences of 26 HBV/A isolates, originating from eight Brazilian states, were determined. All were adw2. Twenty-three belonged to subgenotype A1 and three to A2. By phylogenetic analysis, it was shown t...
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