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Current Opinion in Virology

Wenwen Liu, Jamal-U-Ddin Hajano, Xifeng Wang
Tenuiviruses, which cause serious diseases in rice, wheat, maize and other gramineae crops, recently have been assigned to the family Phenuiviridae in the order Bunyavirales. Transmission of tenuiviruses to host plants depends on the specific vector planthoppers. The interaction between the virus and insect offers critical points for developing an efficient management strategy. This review focuses on recent advancements in our understanding of the interactions between the virus and insect components. Vector components such as various proteins play major roles in virus replication, stability and transovarial transmission...
July 17, 2018: Current Opinion in Virology
Ben Berkhout
RNA interference (RNAi) was discovered in plants where it functions as the main antiviral pathway and this antiviral role was subsequently extended to invertebrates. But it remained hotly debated whether RNAi fulfils a similar role in mammals that already have a potent innate immune system based on interferon and an elaborate adaptive immune system. On the one hand, mammalian cells do encode most of the RNAi machinery, but this could be used exclusively to control cellular gene expression via micro RNAs (miRNAs)...
July 14, 2018: Current Opinion in Virology
Avraham Bayer, Greg Brennan, Adam P Geballe
Viruses evolve rapidly in response to host defenses and to exploit new niches. Gene amplification, a common adaptive mechanism in prokaryotes, archaea, and eukaryotes, has also contributed to viral evolution, especially of large DNA viruses. In experimental systems, gene amplification is one mechanism for rapidly overcoming selective pressures. Because the amplification generally incurs a fitness cost, emergence of adaptive point mutations within the amplified locus or elsewhere in the genome can enable collapse of the locus back to a single copy...
July 13, 2018: Current Opinion in Virology
Rafael Sanjuán
Individual virions typically fail to infect cells. Such decoupling between virions and infectious units is most evident in multicomponent and other segmented viruses, but is also frequent in non-segmented viruses. Despite being a well-known observation, the causes and implications of low single-virion infectivity often remain unclear. In principle, this can originate from intrinsic genetic and/or structural virion defects, but also from host infection barriers that limit early viral proliferation. Hence, viruses may have evolved strategies to increase the per-virion likelihood of establishing successful infections...
July 12, 2018: Current Opinion in Virology
Ahmed Mahas, Magdy Mahfouz
In prokaryotes, CRISPR/Cas adaptive immunity systems target and destroy nucleic acids derived from invading bacteriophages and other foreign genetic elements. In eukaryotes, the native function of these systems has been exploited to combat viruses in mammals and plants. Rewired CRISPR/Cas9 and CRISPR/Cas13 systems have been used to confer resistance against DNA and RNA viruses, respectively. Here, we discuss recent approaches employing CRISPR/Cas systems to combat viruses in eukaryotes, highlight key challenges, and provide future perspectives...
July 10, 2018: Current Opinion in Virology
Enrico Malito, Sumana Chandramouli, Andrea Carfi
The 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 structure, conformational flexibility, location of epitopes for neutralizing antibodies and potential binding sites for cell surface receptors...
June 1, 2018: Current Opinion in Virology
Ronja Pogan, Jasmin Dülfer, Charlotte Uetrecht
Noroviruses are rapidly evolving RNA viruses and are generally known as the main cause of viral gastroenteritis worldwide. Particle stability is of special interest as transmission occurs via the faecal-oral route and virions are able to persist in the environment. Studies on norovirus capsid assembly and disassembly rely mainly on norovirus-like particles. Notably, stability of several human, murine and bovine variants has been investigated revealing distinct patterns of stability and also distinct assembly mechanisms and intermediates...
May 29, 2018: Current Opinion in Virology
Kathryn M Hastie, Erica Ollmann Saphire
The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery...
May 26, 2018: Current Opinion in Virology
Stefan Taube, Alvaro Mallagaray, Thomas Peters
Noroviruses engage glycans as essential attachment factors to promote infection of host cells. The past decade has witnessed significant progress in the field of norovirus research. Cell culture systems and animal models have become available, and structural biology and biophysics have significantly expanded our understanding of norovirus-glycan interactions. From crystallography, many high-resolution crystal structures are now available disclosing key elements of glycan recognition at atomic resolution. On this basis, NMR spectroscopy, native mass spectrometry, and biophysical techniques targeting membrane attached glycans have raised more intricate questions about the nature of norovirus-glycan attachment implying that a static picture of glycan recognition is insufficient...
May 10, 2018: Current Opinion in Virology
Stephan Urban, Antonio Bertoletti
No abstract text is available yet for this article.
June 2018: Current Opinion in Virology
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The 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 drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
June 2018: Current Opinion in Virology
Thomas Tu, Stephan Urban
While chronic infection with the human hepatitis B virus (HBV) and hepatitis delta virus (HDV) inflict major health burdens worldwide, current therapies cannot cure patients. One possible novel approach is blocking virus entry to prevent the establishment of infection in naïve hepatocytes. As HBV and HDV use identical viral envelope proteins and the same entry mechanisms, such a strategy would target both viruses. Entry inhibitors (e.g. neutralizing antibodies) have been relegated to the limited role of prophylaxis...
June 2018: Current Opinion in Virology
Claudia Dembek, Ulrike Protzer, Michael Roggendorf
The 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 suboptimal vaccine design...
June 2018: Current Opinion in Virology
Davide Corti, Fabio Benigni, Daniel Shouval
While 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 neutralizing anti-HBs antibodies have been shown to protect against HBV challenge...
June 2018: Current Opinion in Virology
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 recommendations for treatment. Emerging non-invasive biomarkers of disease activity will further enhance disease stratification...
June 2018: Current Opinion in Virology
Betty L Slagle, Michael J Bouchard
Chronic 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 different functions of HBx are needed, depending on the changing hepatocyte environment encountered during a chronic virus infection, and that these functions might serve as novel therapeutic targets for inhibiting hepatitis B virus replication and the development of associated diseases...
June 2018: Current Opinion in Virology
Magnus Lindh, Gustaf E Rydell, Simon B Larsson
A 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 continue to produce large amounts of HBsAg...
June 2018: Current Opinion in Virology
Christoph Seeger
Chronic hepatitis B virus infections affect over 250 million people world-wide, and, at present, are not curable. Of those, over 800000 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 inhibit de novo virus production by inhibiting the viral reverse transcriptase and, as a consequence, reducing virus titers...
June 2018: Current Opinion in Virology
Aleksei Suslov, Stefan Wieland, Stephan Menne
The 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. Interestingly, hepatitis B virus (HBV) seems to act like a stealth virus that escapes cell intrinsic antiviral mechanisms through avoiding recognition by the innate system rather than blocking its effector functions...
June 2018: Current Opinion in Virology
Paola Fisicaro, Carolina Boni, Valeria Barili, Diletta Laccabue, Carlo Ferrari
HBV-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/sequential use of compounds able to induce decline of antigen load, checkpoint modulation, metabolic and epigenetic reprogramming with possible boosting of functionally restored responses by specific vaccines...
June 2018: Current Opinion in Virology
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