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Cell Communication and Signaling : CCS Sep 2023Cholesterol plays a significant role in stabilizing lipid or membrane rafts, which are specific cellular membrane structures. Cholesterol is involved in numerous... (Review)
Review
Cholesterol plays a significant role in stabilizing lipid or membrane rafts, which are specific cellular membrane structures. Cholesterol is involved in numerous cellular processes, including regulating virus entry into the host cell. Multiple viruses have been shown to rely on cholesterol for virus entry and/or morphogenesis. Research indicates that reprogramming of the host's lipid metabolism is associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the progression to severe liver disease for viruses that cause chronic hepatitis. Moreover, knowing the precise mode of viral interaction with target cells sheds light on viral pathogenesis and aids in the development of vaccines and therapeutic targets. As a result, the area of cholesterol-lowering therapy is quickly evolving and has many novel antiviral targets and medications. It has been shown that microRNAs (miRNAs) either directly or indirectly target the viral genome, preventing viral replication. Moreover, miRNAs have recently been shown to be strong post-transcriptional regulators of the genes involved in lipid metabolism, particularly those involved in cholesterol homeostasis. As important regulators of lipid homeostasis in several viral infections, miRNAs have recently come to light. In addition, multiple studies demonstrated that during viral infection, miRNAs modulate several enzymes in the mevalonate/cholesterol pathway. As cholesterol metabolism is essential to the life cycle of viral hepatitis and other viruses, a sophisticated understanding of miRNA regulation may contribute to the development of a novel anti-HCV treatment. The mechanisms underlying the effectiveness of miRNAs as cholesterol regulators against viral hepatitis are explored in this review. Video Abstract.
Topics: Humans; Antibodies; Cell Membrane; Cholesterol; Hepatitis B virus; Hepatitis, Viral, Human
PubMed: 37710249
DOI: 10.1186/s12964-023-01250-w -
Viruses May 2024Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections... (Review)
Review
Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections are recorded annually, especially in poorly resourced places which have lax vaccination policies. Again, as HBV has no cure and chronic infection is lifelong, vaccines cannot help those already infected. Studies to thoroughly understand the HBV biology and pathogenesis are limited, leaving much yet to be understood about the genomic features and their role in establishing and maintaining infection. The current knowledge of the impact on disease progression and response to treatment, especially in hyperendemic regions, is inadequate. This calls for in-depth studies on viral biology, mainly for the purposes of coming up with better management strategies for infected people and more effective preventative measures for others. This information could also point us in the direction of a cure. Here, we discuss the progress made in understanding the genomic basis of viral activities leading to the complex interplay of the virus and the host, which determines the outcome of HBV infection as well as the impact of coinfections.
Topics: Humans; Hepatitis B virus; Hepatitis B; Coinfection; Genome, Viral; Animals
PubMed: 38793606
DOI: 10.3390/v16050724 -
World Journal of Gastroenterology Mar 2022Chronic hepatitis B virus (HBV) infection is an international health problem with extremely high mortality and morbidity rates. Although current clinical chronic... (Review)
Review
Chronic hepatitis B virus (HBV) infection is an international health problem with extremely high mortality and morbidity rates. Although current clinical chronic hepatitis B (CHB) treatment strategies can partly inhibit and eliminate HBV, viral breakthrough may result due to non-adherence to treatment, the emergence of viral resistance, and a long treatment cycle. Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems. Therefore, understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control. This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.
Topics: Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Humans
PubMed: 35317051
DOI: 10.3748/wjg.v28.i9.881 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2022Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the...
Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.
Topics: Hepatitis B virus; Humans; Immunotherapy; Risk Factors
PubMed: 35788533
DOI: 10.7507/1001-5515.202112003 -
Liver International : Official Journal... Mar 2023
Topics: Humans; Hepatitis B virus; Antiviral Agents; Virus Replication
PubMed: 36808695
DOI: 10.1111/liv.15522 -
Journal of Medical Virology May 2018Hepatitis B virus (HBV) infection represents the most common cause of chronic liver diseases worldwide. Consequently, to the introduction of the universal HBV... (Review)
Review
Hepatitis B virus (HBV) infection represents the most common cause of chronic liver diseases worldwide. Consequently, to the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced and less than 1% of the population of Western Europe and North America is chronically infected. To date, despite great advances in therapeutics, HBV chronic infection is considered an incurable disease. Ten hepatitis B virus genotypes (A-J) and several subgenotypes have been identified so far, based on intergroup divergences of 8% and 4%, respectively, in the complete viral genome. HBV-D genotype has been found throughout the world, with highest prevalence in the Mediterranean area. In the present review, several articles concerning HBV epidemiology, and phylogeny in Italy have been analyzed, mainly focusing on the changes occurred in the last decade.
Topics: Genotype; Hepatitis B virus; Hepatitis B, Chronic; Humans; Italy; Molecular Epidemiology; Phylogeny; Prevalence
PubMed: 29315661
DOI: 10.1002/jmv.25027 -
Journal of Hepatology Jun 2018All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another...
BACKGROUND & AIMS
All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear.
METHODS
We analysed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools, and conducted evolutionary analyses.
RESULTS
We identified a novel orthohepadnavirus species in capuchin monkeys (capuchin monkey hepatitis B virus [CMHBV]). We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal. Non-inflammatory, probably chronic infection was consistent with an intact preCore domain, low genetic variability, core deletions in deep sequencing, and no elevated liver enzymes. Cross-reactivity of antisera against surface antigens suggested antigenic relatedness of HBV, CMHBV, and WMHBV. Infection-determining CMHBV surface peptides bound to the human HBV receptor (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the human sodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that cross-species infections may be possible. Ancestral state reconstructions and sequence distance comparisons associated HBV with humans, whereas primate hepadnaviruses as a whole were projected to NHP ancestors. Co-phylogenetic analyses yielded evidence for co-speciation of hepadnaviruses and New World NHP. Bayesian hypothesis testing yielded strong support for an association of the HBV stem lineage with hominoid ancestors. Neither CMHBV nor WMHBV was likely the ancestor of the divergent human HBV genotypes F/H found in American natives.
CONCLUSIONS
Our data suggest ancestral co-speciation of hepadnaviruses and NHP, and an Old World origin of the divergent HBV genotypes F/H. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B.
LAY SUMMARY
The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.
Topics: Amino Acid Sequence; Animals; Bayes Theorem; Brazil; Cebus; Evolution, Molecular; Genetic Speciation; Genome, Viral; Hepatitis B; Hepatitis B Antigens; Hepatitis B virus; Host Microbial Interactions; Humans; Models, Genetic; Monkey Diseases; Organic Anion Transporters, Sodium-Dependent; Orthohepadnavirus; Phylogeny; Primates; Receptors, Virus; Symporters; Virus Internalization
PubMed: 29428874
DOI: 10.1016/j.jhep.2018.01.029 -
Viruses May 2016The Hepadnaviridae family of small, enveloped DNA viruses are characterized by a strict host range and hepatocyte tropism. The prototype hepatitis B virus (HBV) is a... (Review)
Review
The Hepadnaviridae family of small, enveloped DNA viruses are characterized by a strict host range and hepatocyte tropism. The prototype hepatitis B virus (HBV) is a major human pathogen and constitutes a public health problem, especially in high-incidence areas. Reporter-expressing recombinant viruses are powerful tools in both studies of basic virology and development of antiviral therapeutics. In addition, the highly restricted tropism of HBV for human hepatocytes makes it an ideal tool for hepatocyte-targeting in vivo applications such as liver-specific gene delivery. However, compact genome organization and complex replication mechanisms of hepadnaviruses have made it difficult to engineer replication-competent recombinant viruses that express biologically-relevant cargo genes. This review analyzes difficulties associated with recombinant hepadnavirus vector development, summarizes and compares the progress made in this field both historically and recently, and discusses future perspectives regarding both vector design and application.
Topics: Genes, Reporter; Genetic Vectors; Hepatitis B virus; Humans; Staining and Labeling; Virology
PubMed: 27171106
DOI: 10.3390/v8050125 -
Viruses May 2024The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense... (Review)
Review
The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense and restrict viral replication by impeding multiple steps during its intracellular lifecycle. This review summarizes many of the well-described restriction factors, their mechanisms of restriction, and counteractive measures of HBV, with a special focus on viral transcription. We discuss some of the limitations and knowledge gaps about the restriction factors, highlighting how these factors may be harnessed to facilitate therapeutic strategies against HBV.
Topics: Hepatitis B virus; Virus Replication; Humans; Host-Pathogen Interactions; Hepatitis B; Hepatocytes; Animals
PubMed: 38793645
DOI: 10.3390/v16050764 -
Clinical Gastroenterology and... Jan 2020
Topics: Hepatitis B virus; Humans; Infections
PubMed: 31252194
DOI: 10.1016/j.cgh.2019.06.026