TY - JOUR AB - Despite the growing interest in the microbiome in recent years, the study of the virome, the major part of which is made up of bacteriophages, is relatively underdeveloped compared with their bacterial counterparts. This is due in part to the lack of a universally conserved marker such as the 16S rRNA gene. For this reason, the development of metagenomic approaches was a major milestone in the study of the viruses in the microbiome or virome. However, it has become increasingly clear that these wet-lab methods have not yet been able to detect the full range of viruses present, and our understanding of the composition of the virome remains incomplete. In recent years, a range of new technologies has been developed to further our understanding. Direct RNA-Seq technologies bypass the need for cDNA synthesis, thus avoiding biases subjected to this step, which further expands our understanding of RNA viruses. The new generation of amplification methods could solve the low biomass issue relevant to most virome samples while reducing the error rate and biases caused by whole genome amplification. The application of long-read sequencing to virome samples can resolve the shortcomings of short-read sequencing in generating complete viral genomes and avoid the biases introduced by the assembly. Novel experimental methods developed to measure viruses' host range can help overcome the challenges of assigning hosts to many phages, specifically unculturable ones. AU - Smith, S. AU - Huang, W. AU - Tiamani, K. AU - Unterer, M. AU - Khan Mirzaei, M. AU - Deng, L. C1 - 65476 C2 - 52702 TI - Emerging technologies in the study of the virome. JO - Curr. Opin. Virol. VL - 54 PY - 2022 SN - 1879-6257 ER - TY - JOUR AB - 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. A main obstacle in chronic hepatitis B, however, is the high load of viral antigens expressed and secreted, which has been proposed to cause antigen-specific immune tolerance. Reduction of the viral antigen load is therefore considered a key factor for success of immune-based therapies. Although nucleoside analogs do not reduce viral antigen expression, new antiviral strategies are becoming available. Targeting viral translation by siRNA or targeting release of HBsAg from infected hepatocytes by nucleic acid polymers both reduce the antigen load. They may be considered as pre-treatment for therapeutic vaccination to increase the potential to elicit an HBV-specific immune response able to control and cure chronic HBV infection. AU - Dembek, C.J. AU - Protzer, U. AU - Roggendorf, M. C1 - 53506 C2 - 44881 SP - 58-67 TI - Overcoming immune tolerance in chronic hepatitis B by therapeutic vaccination. JO - Curr. Opin. Virol. VL - 30 PY - 2018 SN - 1879-6257 ER - TY - JOUR AB - Hepatitis B virus (HBV) infection is a global health threat with 240 million chronic carriers at high risk to develop hepatocellular carcinoma. Current antiviral treatment can efficiently control viral replication and reduce liver inflammation, but is still quite far from achieving a cure. Significant progress has been made in understanding the virus life cycle and virus-host interaction in the past few years. With identification of the HBV receptor, cell-culture infection systems have become available that allow drug screening and establishing a pipeline of potential antivirals targeting either viral or host factors. Most of the candidate antivirals summarized in this review are still in preclinical development, but some have already entered or are about to enter early clinical trials. AU - Ko, C. AU - Michler, T. AU - Protzer, U. C1 - 50973 C2 - 43026 CY - Oxford SP - 38-45 TI - Novel viral and host targets to cure hepatitis B. JO - Curr. Opin. Virol. VL - 24 PB - Elsevier Sci Ltd PY - 2017 SN - 1879-6257 ER - TY - JOUR AB - A therapeutic vaccine is meant to activate the patient's immune system to fight and finally control or ideally eliminate an already established infectious pathogen. Whereas the success of prophylactic vaccination is based on rapid antibody-mediated neutralization of an invading pathogen, control and elimination of persistent viruses such as hepatitis, herpes or papilloma viruses requires multi-specific and polyfunctional effector T cell responses. These are ideally directed against continuously expressed viral antigens to keep the pathogen in check. Activation of a humoral immune response in order to lower viral antigen load and to limit virus spread, however, confers an additional benefit. Therapeutic vaccines are under development for a number of chronic infections and require an intelligent vaccine design. Hepatitis B virus (HBV) infection may serve as a prime example since a spontaneous, immune-mediated recovery of chronic hepatitis B and an elimination of the virus is possible even if it is observed only in very rare cases. In this review, we summarize the current knowledge and potential improvements of therapeutic vaccines for chronic hepatitis B. AU - Kosinska, A. AU - Bauer, T. AU - Protzer, U. C1 - 51013 C2 - 42644 CY - Oxford SP - 75-81 TI - Therapeutic vaccination for chronic hepatitis B. JO - Curr. Opin. Virol. VL - 23 PB - Elsevier Sci Ltd PY - 2017 SN - 1879-6257 ER - TY - JOUR AB - EBV drives resting B cells to continuous proliferating latently infected cells. A restricted program of viral transcription contributes to latency and cell proliferation important for growth transformation. Recent interest in latency and transformation has provided new data about the roles of the EBV encoded latent proteins and non-coding RNAs. We broadly describe the transcription, epigenetic, signaling and super-enhancer functions of the latent nuclear antigens in regulating cellular transcription; the role of LMP2 in utilization of the autophagosome to control cell death, and the association between LMP1, the linear ubiquitin chain assembly complex and TRAF1 which are important for transformation. This review explores recent discoveries with new insights into therapeutic avenues for EBV related malignancies. AU - Kempkes, B. AU - Robertson, E.S.* C1 - 47098 C2 - 39140 SP - 138-144 TI - Epstein-Barr virus latency: Current and future perspectives. JO - Curr. Opin. Virol. VL - 14 PY - 2015 SN - 1879-6257 ER - TY - JOUR AB - Due to the limited treatment options hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death, and hepatitis B virus (HBV) infection is the major risk factor for development of HCC worldwide. HCC is typically preceded by chronic inflammation, but may also develop in the absence of liver disease on the basis of HBV infection and even when virus replication is controlled by antivirals. In this situation, HBV antigen expression persists and direct oncogenic effects of HBV are integration of the viral DNA into the host genome as well as direct effects of viral proteins. These factors have to be taken into account in order to personalize HCC surveillance in CHB and unravel novel therapeutic approaches. AU - Ringelhan, M. AU - Protzer, U. C1 - 47259 C2 - 39295 SP - 109-115 TI - Oncogenic potential of hepatitis B virus encoded proteins. JO - Curr. Opin. Virol. VL - 14 PY - 2015 SN - 1879-6257 ER - TY - JOUR AB - Epigenetic mechanisms govern the different life phases of Epstein-Barr virus (EBV). In the first prelatent phase the viral DNA acquires nucleosomes, histone marks are established, and 5'-methyl cytosine residues become detectable. In the latent phase repressive histone marks and extensive DNA methylation silence the majority of viral promoters sparing a few latent genes. DNA methylation is a prerequisite for the induction of EBV's lytic phase in order to escape from latency and give rise to viral progeny. All three phases rely on the different epigenetic states of viral DNA and the availability of viral and cellular factors. EBV exploits cellular mechanisms of epigenetic regulation for its different life phases and serves as a marvelous example of an intimate host-pathogen relationship. AU - Woellmer, A. AU - Hammerschmidt, W. C1 - 26060 C2 - 32049 SP - 260-265 TI - Epstein-Barr virus and host cell methylation: Regulation of latency, replication and virus reactivation. JO - Curr. Opin. Virol. VL - 3 IS - 3 PB - Elsevier Science PY - 2013 SN - 1879-6257 ER -