From recognition to execution — the HCMV Pentamer from receptor binding to fusion triggering
Publication date: Available online 1 June 2018Source: Current Opinion in VirologyAuthor(s): Enrico Malito, Sumana Chandramouli, Andrea CarfiThe β-herpesvirus human cytomegalovirus (HCMV) is the leading viral cause of neonatal developmental disabilities. In HCMV, the conserved herpesvirus glycoprotein B (gB) mediates membrane fusion between the viral and host cell membranes, whereas the trimeric gH/gL/gO or the pentameric gH/gL/UL128/UL130/UL31A complexes (Pentamer) bind to cell-specific receptors and provide the triggering signal to gB. Recent structural and functional studies have provided new insights into Pentamer stru...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Editors-Board-Issue sections
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): (Source: Current Opinion in Virology)
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Contents
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): (Source: Current Opinion in Virology)
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Editorial overview: Antiviral strategies: Virological and immunological basis for HBV cure
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Stephan Urban, Antonio Bertoletti (Source: Current Opinion in Virology)
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Overcoming immune tolerance in chronic hepatitis B by therapeutic vaccination
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Claudia Dembek, Ulrike Protzer, Michael RoggendorfThe currently used nucleoside analogs (i.e. entecavir and tenofovir) with high barrier-to-resistance efficiently suppress viral replication, limit inflammation and reduce the sequelae of chronic hepatitis B, but cannot cure the disease and thus have to be applied long-term. Therapeutic vaccination as an approach to cure chronic hepatitis B has shown promising pre-clinical results, nevertheless the proof of its efficacy in clinical trials is still missing. This may be partially due to subopti...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Modulators of innate immunity as novel therapeutics for treatment of chronic hepatitis B
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Aleksei Suslov, Stefan Wieland, Stephan MenneThe first line defense mechanisms against viral infection are mediated by the innate immune system. Viral components are detected by infected cells and/or innate immune cells that express different sensory receptors. They in turn mediate induction of direct antiviral mechanisms and further modulation of innate and adaptive immune responses. For evading the innate system, most viruses have evolved efficient mechanisms to block sensing and/or antiviral functions of the innate response. Interestingl...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Control of viral transcripts as a concept for future HBV therapies
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Christoph SeegerChronic hepatitis B virus infections affect over 250 million people world-wide, and, at present, are not curable. Of those, over 800 000 are expected to die yearly from complications including cirrhosis and primary hepatocellular carcinoma (HCC). A viral episomal DNA intermediate, covalently closed circular DNA (cccDNA) can persist in nuclei of infected hepatocytes and trigger production of infectious virus. Current standard of care treatments against chronic HBV infections primarily rely on nucleoside analogs (NA) that...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Impact of integrated viral DNA on the goal to clear hepatitis B surface antigen with different therapeutic strategies
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Magnus Lindh, Gustaf E Rydell, Simon B LarssonA hallmark of hepatitis B virus (HBV) infection is the presence of hepatitis B surface antigen (HBsAg) in the serum of patients. Sustained loss of HBV DNA and HBsAg from the blood are main goals for treatment, and considered as functional cure. It is rarely achieved with long-term nucleoside analogue treatment though, both because cccDNA, the template for viral replication, is not completely cleared, and probably also because hepatocytes with HBV DNA integrated into their chromosomes persist and...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Role of HBx in hepatitis B virus persistence and its therapeutic implications
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Betty L Slagle, Michael J BouchardChronic hepatitis B virus infection is a significant risk factor for cirrhosis and hepatocellular carcinoma. The HBx protein is required for virus replication, but the lack of robust infection models has hindered our understanding of HBx functions that could be targeted for antiviral purposes. We briefly review three properties of HBx: its binding to DDB1 and its regulation of cell survival and metabolism, to illustrate how a single viral protein can have multiple effects in a cell. We propose that differen...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Why, who and when to start treatment for chronic hepatitis B infection
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Grace E Dolman, Apostolos Koffas, William S Mason, Patrick TF KennedyChronic hepatitis B remains a major global health challenge due to morbidity and mortality from hepatocellular carcinoma and complications of liver cirrhosis. Current treatment regimens are non-curative and, once initiated, treatment is of indefinite duration for the majority. The decision to initiate treatment decisions is based on risk stratification.Advances in our understanding of the natural history of chronic hepatitis B have led to a paradigm shift in recommendation...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Viral envelope-specific antibodies in chronic hepatitis B virus infection
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Davide Corti, Fabio Benigni, Daniel ShouvalWhile the cellular immune response associated with acute and chronic HBV infection has been thoroughly studied, the B cell response in chronic hepatitis B and the role of antibodies raised against the HBV envelope antigens in controlling and prevention of infection requires further investigation. The detection of anti-HBs antibodies is considered as one of the biomarkers for functional cure of chronic hepatitis B virus infection, as well as for protective immunity. Indeed, vaccine-induced neutraliz...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Perspectives and limitations for nucleo(t)side analogs in future HBV therapies
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien ZoulimThe latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Strategies to overcome HBV-specific T cell exhaustion: checkpoint inhibitors and metabolic re-programming
Publication date: June 2018Source: Current Opinion in Virology, Volume 30Author(s): Paola Fisicaro, Carolina Boni, Valeria Barili, Diletta Laccabue, Carlo FerrariHBV-specific T cells play a key role in antiviral protection and failure to control HBV is associated with severely dysfunctional T cell responses. Therefore, functional T cell reconstitution represents a potential way to treat chronically infected patients. The growing understanding of the dysregulated transcriptional/epigenetic and metabolic programs underlying T cell exhaustion allows to envisage functional T cell reconstitution strategies based on the combined...
Source: Current Opinion in Virology - July 5, 2018 Category: Virology Source Type: research
Human organoid cultures: transformative new tools for human virus studies
Publication date: April 2018 Source:Current Opinion in Virology, Volume 29 Author(s): Sasirekha Ramani, Sue E Crawford, Sarah E Blutt, Mary K Estes Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host–microbe interactions. Here, we summariz...
Source: Current Opinion in Virology - April 13, 2018 Category: Virology Source Type: research
Why, who and when to start treatment for chronic hepatitis B infection
Publication date: June 2018 Source:Current Opinion in Virology, Volume 30 Author(s): Grace E Dolman, Apostolos Koffas, William S Mason, Patrick TF Kennedy Chronic hepatitis B remains a major global health challenge due to morbidity and mortality from hepatocellular carcinoma and complications of liver cirrhosis. Current treatment regimens are non-curative and, once initiated, treatment is of indefinite duration for the majority. The decision to initiate treatment decisions is based on risk stratification. Advances in our understanding of the natural history of chronic hepatitis B have led to a paradigm shift in recom...
Source: Current Opinion in Virology - April 12, 2018 Category: Virology Source Type: research
