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Zeitschrift Fur Gastroenterologie Jul 2021
Topics: Gastroenterology; Hepatitis B; Hepatitis B virus; Humans; Metabolic Diseases
PubMed: 34255313
DOI: 10.1055/a-1498-2706 -
Advances in Experimental Medicine and... 2020Hepatitis B virus (HBV) is a major human pathogen lacking a reliable curative therapy. Current therapeutics target the viral reverse transcriptase/DNA polymerase to... (Review)
Review
Hepatitis B virus (HBV) is a major human pathogen lacking a reliable curative therapy. Current therapeutics target the viral reverse transcriptase/DNA polymerase to inhibit viral replication but generally fail to resolve chronic HBV infections. Due to the limited coding potential of the HBV genome, alternative approaches for the treatment of chronic infections are desperately needed. An alternative approach to the development of antiviral therapeutics is to target cellular gene products that are critical to the viral life cycle. As transcription of the viral genome is an essential step in the viral life cycle, the selective inhibition of viral RNA synthesis is a possible approach for the development of additional therapeutic modalities that might be used in combination with currently available therapies. To address this possibility, a molecular understanding of the relationship between viral transcription and replication is required. The first step is to identify the transcription factors that are the most critical in controlling the levels of HBV RNA synthesis and to determine their in vivo role in viral biosynthesis. Mapping studies in cell culture utilizing reporter gene constructs permitted the identification of both ubiquitous and liver-enriched transcription factors capable of modulating transcription from the four HBV promoters. However, it was challenging to determine their relative importance for viral biosynthesis in the available human hepatoma replication systems. This technical limitation was addressed, in part, by the development of non-hepatoma HBV replication systems where viral biosynthesis was dependent on complementation with exogenously expressed transcription factors. These systems revealed the importance of specific nuclear receptors and hepatocyte nuclear factor 3 (HNF3)/forkhead box A (FoxA) transcription factors for HBV biosynthesis. Furthermore, using the HBV transgenic mouse model of chronic viral infection, the importance of various nuclear receptors and FoxA isoforms could be established in vivo. The availability of this combination of systems now permits a rational approach toward the development of selective host transcription factor inhibitors. This might permit the development of a new class of therapeutics to aid in the treatment and resolution of chronic HBV infections, which currently affects approximately 1 in 30 individuals worldwide and kills up to a million people annually.
Topics: Animals; DNA, Viral; Hepatitis B virus; Humans; Mice; Transcription, Genetic; Virus Replication
PubMed: 31741333
DOI: 10.1007/978-981-13-9151-4_3 -
Biosensors & Bioelectronics Dec 2021Classical gold standard HBV detection relies on expensive devices and complicated procedures, thus is always restricted in large-scale hospitals and centers for disease...
Classical gold standard HBV detection relies on expensive devices and complicated procedures, thus is always restricted in large-scale hospitals and centers for disease control and prevention. To extend HBV detection to primary clinics especially in underdeveloped areas, we design amplification-free smartphone-based attomolar HBV detecting technique based on single molecule sensing. Verified by synthesized HBV target DNA, this technique reaches a detection limit at attomolar concentration (100 aM); and verified by 110 clinical samples, it also reaches a rather high sensitivity of 10 copy/mL (≈2000 IU/mL) with a high accuracy of 93.64% certificated by gold standard HBV detecting devices. Besides, this technique can quantify HBV viral load in 70 min only using portable and inexpensive devices as well as simple operations. Because of its cost-effective, field-portable and operable design, highly sensitive and selective detecting capability and wireless data connectivity, this technique can be potentially used in mobile HBV diagnoses and share HBV epidemic information especially in resource limited situations.
Topics: Biosensing Techniques; Diagnostic Tests, Routine; Hepatitis B virus; Smartphone; United States; Viral Load
PubMed: 34543826
DOI: 10.1016/j.bios.2021.113622 -
Clinics in Liver Disease Nov 2023The natural history of hepatitis B virus (HBV) infection is closely dependent on the dynamic interplay between the host immune response and viral replication.... (Review)
Review
The natural history of hepatitis B virus (HBV) infection is closely dependent on the dynamic interplay between the host immune response and viral replication. Spontaneous HBV clearance in acute self-limited infection is the result of an adequate and efficient antiviral immune response. Instead, it is widely recognized that in chronic HBV infection, immunologic dysfunction contributes to viral persistence. Long-lasting exposure to high viral antigens, upregulation of multiple co-inhibitory receptors, dysfunctional intracellular signaling pathways and metabolic alterations, and intrahepatic regulatory mechanisms have been described as features ultimately leading to a hierarchical loss of effector functions up to full T-cell exhaustion.
Topics: Humans; Hepatitis B virus; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Hepatitis B; Virus Replication
PubMed: 37778772
DOI: 10.1016/j.cld.2023.05.001 -
Experimental Cell Research Sep 2023The hepatitis B Virus X (HBx) protein plays a crucial role in the HBV-induced hepatic steatosis. Fatty acid transport protein 2 (FATP2) is a key protein that is involved...
The hepatitis B Virus X (HBx) protein plays a crucial role in the HBV-induced hepatic steatosis. Fatty acid transport protein 2 (FATP2) is a key protein that is involved in hepatic lipogenesis, and it was found to be highly expressed in various metabolic diseases. However, Whether FATP2 is a key factor in the pathogenesis of HBx-induced hepatic steatosis remains unclear. In this study, we found that FATP2 was up-regulated by HBx in vitro and in vivo and participated in HBx-induced hepatic lipid accumulation. Treatment of HBx-expressing cell lines and mice with FATP2 inhibitor (FATP2i) lipofermata ameliorated HBx-induced lipid accumulation and reduced oxidative stress and inflammation caused by lipid accumulation. Moreover, the liver injury of mouse was restored after FATP2i treatment. In summary, our results reveal that FATP2 is a key driver factor for HBx-induced hepatic lipid accumulation, and inhibition of FATP2 can ameliorates lipid accumulation caused by HBx. This study provides new insights into the mechanism of HBV-induced hepatic steatosis.
Topics: Mice; Animals; Up-Regulation; Fatty Liver; Cell Line; Lipids; Hepatitis B virus
PubMed: 37437769
DOI: 10.1016/j.yexcr.2023.113721 -
Journal of Hepatology Jul 2021
Topics: Anaerobiosis; Hepatitis B; Hepatitis B virus; Humans
PubMed: 33820670
DOI: 10.1016/j.jhep.2021.03.002 -
Nature Communications Jun 2023Hepatitis B virus (HBV) only infects humans and chimpanzees, posing major challenges for modeling HBV infection and chronic viral hepatitis. The major barrier in...
Hepatitis B virus (HBV) only infects humans and chimpanzees, posing major challenges for modeling HBV infection and chronic viral hepatitis. The major barrier in establishing HBV infection in non-human primates lies at incompatibilities between HBV and simian orthologues of the HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP). Through mutagenesis analysis and screening among NTCP orthologues from Old World monkeys, New World monkeys and prosimians, we determined key residues responsible for viral binding and internalization, respectively and identified marmosets as a suitable candidate for HBV infection. Primary marmoset hepatocytes and induced pluripotent stem cell-derived hepatocyte-like cells support HBV and more efficient woolly monkey HBV (WMHBV) infection. Adapted chimeric HBV genome harboring residues 1-48 of WMHBV preS1 generated here led to a more efficient infection than wild-type HBV in primary and stem cell derived marmoset hepatocytes. Collectively, our data demonstrate that minimal targeted simianization of HBV can break the species barrier in small NHPs, paving the path for an HBV primate model.
Topics: Animals; Humans; Hepatitis B virus; Callithrix; Hepatitis B; Hepatocytes; Virus Attachment; Symporters; Virus Internalization; Hep G2 Cells
PubMed: 37328459
DOI: 10.1038/s41467-023-39148-3 -
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