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Study Of Cell Host Factors Involved In Hepatitis C Virus Tropism
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Book Synopsis Study of Cell Host Factors Involved in Hepatitis C Virus Tropism by : Daniel Da Costa
Download or read book Study of Cell Host Factors Involved in Hepatitis C Virus Tropism written by Daniel Da Costa and published by . This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis C virus (HCV) is a global health burden. The development of new therapeutics to treat HCV infection has been hampered by the lack of convenient in vitro and in vivo model systems. The goal of my PhD work was, in a first time, to characterize the factors determining the hepatotropism of HCV. By expressing key factors within a non-hepatic cell line, we reconstituted in fine the full HCV life cycle in those cells. Virus entry into the host cell requires different entry factors which are CD81, occludin (OCLN), claudin-1 (CLDN1) and the scavenger receptor class B type I (SR-BI). The expression of these four factors in this cell line renders it highly permissive to viral entry, but does not allow restoring replication of the virus. The expression of miR-122, a micro-RNA important for HCV infection, into the cell lines expressing the four HCV entry factors restore a strong replication of the HCV RNA but does not allow detecting infectious viral particle production. Further expression of the apolipoprotein E (apoE), which plays a critical role in the assembly and release process, restore the last step of the HCV life cycle in a non-hepatic cell line. In a second part of my PhD, I have used the previously developed strategy to study the species specificity of HCV infection using different mouse hepatoma cell lines. We have been able to render these cell lines permissive to HCV entry and have been able to detect a slight replication. Altogether, my results bring new information on the understanding of key factors important for HCV life cycle in mouse and human cells.
Book Synopsis Host Factor Regulation of Hepatitis C Virus Replication in Rodent Cells by : Liang-Tzung Lin
Download or read book Host Factor Regulation of Hepatitis C Virus Replication in Rodent Cells written by Liang-Tzung Lin and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Hepatitis C written by Imran Shahid and published by BoD – Books on Demand. This book was released on 2018-10-10 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: The propagation of hepatitis C from acute to chronic infection and afterward to end-stage liver diseases (hepatic fibrosis, cirrhosis, and hepatocellular carcinoma) involves a highly orchestrated series of molecular and cellular events, including a plethora of genes and cell signaling cascades. The treatment paradigms was revolutionized after the development and approval of all oral interferon-free direct-acting antivirals achieving higher sustained virologic response rates in treated individuals. This book pragmatically overviews the intricate interplay between viral and host factors during hepatitis C virus infection progression, as well as other hepatitis C-associated clinical implications. Hepatitis C - From Infection to Cure also provides up-to-date information about hepatitis C cures for clinicians, physicians, and healthcare providers with an ample understanding of the current treatment horizon, as well as other investigational and emerging treatment strategies. The authors with their valuable scientific contributions belong to many eminent institutes around the world and are much experienced in hepatitis C virology, pathology, and therapeutics.
Book Synopsis The Contribution of Viral and Host Cell Factors to Replication of the Hepatitis C Virus RNA Genome by : Daniel M. Jones
Download or read book The Contribution of Viral and Host Cell Factors to Replication of the Hepatitis C Virus RNA Genome written by Daniel M. Jones and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Studies on the hepatitis C virus (HCV) life cycle have been aided by the development of in vitro systems that permit replication of the viral RNA genome and virus particle production. However, the exact functions of the viral proteins, particularly those engaged in RNA synthesis, are poorly understood. It is thought that NS4B, one of the replicase components, induces the formation of replication complexes (RCs) derived from host cell membranes. These RCs appear as punctate foci at the endoplasmic reticulum (ER) membrane and incorporate the viral and cellular proteins necessary for HCV RNA synthesis. To gain insight into the nature of RCs, green fluorescent protein (GFP) was inserted into the coding region of NS5A, one of the HCV-encoded replicase components. The impact of the GFP insertion was examined in the context of a subgenomic replicon (SGR) based on JFH1, a genotype 2a HCV strain that exhibits efficient RNA replication in cell culture. The resulting construct was capable of robust replication and allowed characterisation of NS5A in live cells that synthesised viral RNA. NS5A displayed a diffuse, ER-like distribution and was also observed in foci. These foci are presumed to represent RCs and NS5A was relatively immobile at these sites. This result was confirmed using SGRs harbouring a photoactivatable derivative of GFP (PAGFP). Utilising plasmid-encoded HCV polyproteins, it was apparent that the targeting of NS5A to these structures was dependent on NS4B. Removal of the NS4B coding region resulted in a diffuse, ER-like distribution of NS5A, with little evidence of the protein within RCs. NS5A was mobile under these conditions, suggesting that the dynamics of NS5A are linked to focus formation by NS4B. To further investigate these findings, a panel of 15 alanine substitutions was constructed in the C-terminal region of NS4B. Transient replication assays revealed that five mutants were incapable of replication, two displayed an attenuated phenotype, and eight exhibited replication levels comparable to the wild-type (wt) genome. Of the five non-replicating mutants, two were defective in their ability to produce foci, while one failed to generate any foci. Thus, the C-terminus of NS4B is important for RC formation. Loss of NS4B foci correlated with decreased NS5A located in these structures. Furthermore, NS5A hyperphosphorylation was reduced for mutants compromised in foci production. This suggests that the membranous changes induced by NS4B provide a favourable environment for post-translational modifications of NS5A. Interestingly, the remaining two non-replicating mutants displayed no impairment in foci production and the characteristics of NS5A were also unaltered. Therefore, in addition to producing the cellular environment for HCV genome synthesis, NS4B is likely to play a more direct role in RNA replication. HCV RCs are believed to be relatively enclosed structures that permit limited exchange of materials with the cytoplasm. In support of this hypothesis, previous reports have shown that NS5A is the only replicase component capable of restoring replication to defective genomes when supplied in trans. In those studies, SGRs harbouring replication-lethal NS4B mutations could not be rescued by trans-complementation. Utilising the five novel non-replicating genomes described above, the potential to trans-complement NS4B in transient replication assays was re-examined. Wt protein produced from a functional HCV replicon could trans-complement defective NS4B expressed from two of the five mutants. Moreover, active replication could be reconstituted from two defective viral RNAs harbouring mutations within NS4B and NS5A. These findings have important implications for our understanding of RC formation. Genome-length JFH1 RNA produces infectious virus particles in Huh-7 cells. Using this system, it has become increasingly apparent that some HCV-encoded replication components are also involved in virus assembly and release. To determine whether NS4B had any influence on these latter stages of the virus life cycle, the NS4B mutations that did not block RNA replication were introduced into the full-length JFH1 genome. While the majority of mutants had no effect on virus production, one mutant consistently enhanced infectious virus titres by up to five-fold compared to wt JFH1. Interestingly, introduction of the same mutation into a chimeric J6-JFH1 genome resulted in repressed virion production. Together, these results suggest that NS4B contributes to virus assembly and release in a genotype-specific manner. In an attempt to identify novel cellular proteins involved in HCV genome replication, a siRNA library targeting 299 nucleotide-binding proteins was screened. For the screen, a robust system was established using two cell lines (derived from Huh-7 and U2OS cells) that replicated tri-cistronic SGRs. While the U2OS cell line supported HCV RNA replication less efficiently compared to Huh-7 cells, this cell type was efficiently transfected with siRNA. Consequently, increased gene-silencing and greater effects on HCV replication were observed in the U2OS cell line. Thus, U2OS cells may be a suitable alternative to Huh-7 cells for HCV-related siRNA studies. For the library screen, all siRNAs were tested in both cell lines, and cell viability measurements allowed specific effects on viral RNA synthesis to be characterised. The screen identified several cellular proteins that enhanced and suppressed HCV RNA replication. This study provides an important framework for more detailed analyses of these proteins in the future.
Book Synopsis Saliva Protection and Transmissible Diseases by : Crispian Scully
Download or read book Saliva Protection and Transmissible Diseases written by Crispian Scully and published by Academic Press. This book was released on 2017-07-19 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: Saliva Protection and Transmissible Diseases provides a review of saliva protection, raising debate on micro-organisms potentially transmissible in saliva, and also considering the evidence on diseases that may be transmitted by kissing. Saliva is a complex body fluid essential to health, especially mastication, swallowing and speech, and hyposalivation can lead to dysfunction and even infection. More serious pathogens, such as herpes viruses and papillomaviruses can be conveyed by kissing, as can potentially lethal micro-organisms present in some saliva, such as meningococci, fungal organisms and Ebola viruses. Stipulates the defensive roles of saliva, an important topic not previously reviewed in-depth in literature Provides awareness that saliva also transmits infectious agents that can produce serious or even lethal diseases Gives understanding that kissing may be an at-risk practice
Book Synopsis Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus by : Neda Nasheri Ardekan
Download or read book Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus written by Neda Nasheri Ardekan and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Essential Concepts in Molecular Pathology by : William B. Coleman
Download or read book Essential Concepts in Molecular Pathology written by William B. Coleman and published by Academic Press. This book was released on 2019-11-23 with total page 634 pages. Available in PDF, EPUB and Kindle. Book excerpt: Essential Concepts in Molecular Pathology, Second Edition, offers an introduction to molecular genetics and the "molecular" aspects of human disease. The book illustrates how pathologists harness their understanding of these entities to develop new diagnostics and treatments for various human diseases. This new edition offers pathology, genetics residents, and molecular pathology fellows an advanced understanding of the molecular mechanisms of disease that goes beyond what they learned in medical and graduate school. By bridging molecular concepts of pathogenesis to the clinical expression of disease in cell, tissue and organ, this fully updated, introductory reference provides the background necessary for an understanding of today’s advances in pathology and medicine. Explains the practice of "molecular medicine" and the translational aspects of molecular pathology, including molecular diagnostics, molecular assessment and personalized medicine Orients non-pathologists on what pathologists look for and how they interpret their observational findings based on histopathology Provides the reader with what is missing from most targeted introductions to pathology—the cell biology behind pathophysiology
Book Synopsis Hepatitis C Virus Persistence and Lymphotropism by : Sonya Ann MacParland
Download or read book Hepatitis C Virus Persistence and Lymphotropism written by Sonya Ann MacParland and published by . This book was released on 2010 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Essential Human Virology by : Jennifer Louten
Download or read book Essential Human Virology written by Jennifer Louten and published by Academic Press. This book was released on 2022-05-28 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: Essential Human Virology, Second Edition focuses on the structure and classification of viruses, virus transmission and virus replication strategies based upon type of viral nucleic acid. Several chapters focus on notable and recognizable viruses and the diseases caused by them, including influenza, HIV, hepatitis viruses, poliovirus, herpesviruses and emerging and dangerous viruses. Additionally, how viruses cause disease (pathogenesis) is highlighted, along with discussions on immune response to viruses, vaccines, anti-viral drugs, gene therapy, the beneficial uses of viruses, research laboratory assays and viral diagnosis assays. Fully revised and updated with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses, the book provides students with a solid foundation in virology. Focuses on human diseases and the cellular pathology that viruses cause Highlights current and cutting-edge technology and associated issues Presents real case studies and current news highlights in each chapter Features dynamic illustrations, chapter assessment questions, key terms, and a summary of concepts, as well as an instructor website with lecture slides, a test bank and recommended activities Updated and revised, with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses
Book Synopsis Virus Bioinformatics by : Manja Marz
Download or read book Virus Bioinformatics written by Manja Marz and published by MDPI. This book was released on 2020-02-21 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Virus bioinformatics is evolving and succeeding as an area of research in its own right, representing the interface of virology and computer science. Bioinformatic approaches to investigate viral infections and outbreaks have become central to virology research, and have been successfully used to detect, control, and treat infections of humans and animals. As part of the Third Annual Meeting of the European Virus Bioinformatics Center (EVBC), we have published this Special Issue on Virus Bioinformatics.
Book Synopsis Molecular Virology of Human Pathogenic Viruses by : Wang-Shick Ryu
Download or read book Molecular Virology of Human Pathogenic Viruses written by Wang-Shick Ryu and published by Academic Press. This book was released on 2016-03-30 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Virology of Human Pathogenic Viruses presents robust coverage of the key principles of molecular virology while emphasizing virus family structure and providing key context points for topical advances in the field. The book is organized in a logical manner to aid in student discoverability and comprehension and is based on the author’s more than 20 years of teaching experience. Each chapter will describe the viral life cycle covering the order of classification, virion and genome structure, viral proteins, life cycle, and the effect on host and an emphasis on virus-host interaction is conveyed throughout the text. Molecular Virology of Human Pathogenic Viruses provides essential information for students and professionals in virology, molecular biology, microbiology, infectious disease, and immunology and contains outstanding features such as study questions and recommended journal articles with perspectives at the end of each chapter to assist students with scientific inquiries and in reading primary literature. Presents viruses within their family structure Contains recommended journal articles with perspectives to put primary literature in context Includes integrated recommended reading references within each chapter Provides access to online ancillary package inclusive of annotated PowerPoint images, instructor’s manual, study guide, and test bank
Book Synopsis Viral Pathogenesis by : Michael G. Katze
Download or read book Viral Pathogenesis written by Michael G. Katze and published by Academic Press. This book was released on 2015-12-30 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Pathogenesis: From Basics to Systems Biology, Third Edition, has been thoroughly updated to cover topical advances in the evolving field of viral pathogenesis, while also providing the requisite classic foundational information for which it is recognized. The book provides key coverage of the newfound ability to profile molecular events on a system-wide scale, which has led to a deeper understanding of virus-host interactions, host signaling and molecular-interaction networks, and the role of host genetics in determining disease outcome. In addition, the content has been augmented with short chapters on seminal breakthroughs and profiles of their progenitors, as well as short commentaries on important or controversial issues in the field. Thus, the reader will be given a view of virology research with perspectives on issues such as biomedical ethics, public health policy, and human health. In summary, the third edition will give the student a sense of the exciting new perspectives on viral pathogenesis that have been provided by recent developments in genomics, computation, modeling, and systems biology. Covers all aspects of viral infection, including viral entry, replication, and release, as well as innate and adaptive immunity and viral pathogenesis Provides a fresh perspective on the approaches used to understand how viruses cause disease Features molecular profiling techniques, whole genome sequencing, and innovative computational methods Highlights the use of contemporary approaches and the insights they provide to the field
Book Synopsis Enteric Hepatitis Viruses by : Stanley M. Lemon
Download or read book Enteric Hepatitis Viruses written by Stanley M. Lemon and published by Perspectives Cshl. This book was released on 2018 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: "A subject collection from Cold Spring Harbor Perspectives in Medicine"--title page.
Book Synopsis Investigating Hepatitis C Virus Interactions with Host Lipid Pathways that are Critical for Viral Propagation Using Small Molecule Inhibitors and Chemical Biology Methods by : Rodney Lyn
Download or read book Investigating Hepatitis C Virus Interactions with Host Lipid Pathways that are Critical for Viral Propagation Using Small Molecule Inhibitors and Chemical Biology Methods written by Rodney Lyn and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis C virus (HCV) is remarkably capable of efficiently hijacking host cell pathways including lipid metabolism in the liver in order to create pro-viral environments for pathogenesis. It is becoming increasingly clear that identifying small molecule inhibitors that target host factors exploited by the virus will expand available HCV treatment options. As such, a thorough understanding of host-virus interactions is critical to the development of alternative therapeutic strategies. Hepatic lipid droplets (LDs) are recruited by HCV to play essential roles in the viral lifecycle. The intracellular location of LDs is modified upon interacting with viral structural core protein. This enables formation of platforms that support viral particle assembly. Because these interactions are non-static, capturing its dynamic processes in order to better understand viral assembly can be achieved with label-free molecular imaging enhanced with live-cell capabilities. Chemical biology approaches that includes CARS microscopy employed in a multi-modal imaging system was used to probe interactions between HCV and host LDs. By successfully tracking LD trajectories, we identified core protein's ability to alter LD speed and control for LD directionality. Using protein expression model systems that allowed for simultaneous tracking of core protein and LDs, our data revealed that mutations in the core protein region that vary in hydrophobicity and LD binding strengths, are factors that control for differential modulation of LD kinetics. Furthermore, we measured bidirectional LD travels runs and velocities, and observed critical properties by which core protein induces LD migration towards regions of viral particle assembly. Given that many steps in the HCV lifecycle are directly linked to host lipid metabolism, it is not surprising that disrupting lipid biosynthetic pathways would negatively affect viral replication. From this outlook, we explored small molecule inhibitors that targeted several lipid metabolic pathways to study its antiviral properties. Using fluorescent probes covalently labeled to viral RNA, we captured the visualization of disrupted replication complexes upon antagonizing nuclear hormone receptors that are linked to regulating lipid homeostasis. Correspondingly, biochemistry and molecular imaging techniques were also employed to identify novel antiviral mechanisms of small molecule inhibitors that target additional HCV-dependent lipid metabolic pathways.
Book Synopsis Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease by : A. Graham Pockley
Download or read book Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease written by A. Graham Pockley and published by Springer Science & Business Media. This book was released on 2009-11-10 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease provides the most current review of the literature relating to the role and influence of heat shock (stress) proteins on the establishment, progression and resolution of infectious disease. Written by leaders in the field of heat shock proteins (HSP) and their biological and immunological properties, the contributors provide a fascinating insight into the complex relationship between, and the involvement of prokaryotic and eukaryotic HSP in disease states. It has been known for some considerable time that heat shock proteins from prokaryotic organisms are immunodominant molecules that are intimately involved in the induction of potential protective inflammatory responses, and this aspect of HSP biology is updated herein. In addition to regulating heat shock protein gene expression, the transcription factor HSF1 also appears to play an important role in regulating immune responses to infection. Heat shock proteins are now known to influence infectious disease processes in a number of diverse ways: they are involved in the propagation of prions, the replication and morphogenesis of viruses, and the resistance of parasites to chemotherapy. These proteins also appear to be important mediators of bacteria-host interactions and inflammation, the latter via interactions with cell surface molecules and structures such as Toll-like receptors and lipid rafts. Heat shock proteins can be expressed on the surface of infected cells, and this is likely to provide a target for the innate immune response. Elevated levels of circulating HSP are present in infectious diseases and these proteins might therefore regulate inflammatory responses to pathogenic challenge on a systemic basis. Heat shock proteins are also implicated in the impact of genital tract infections on the reproductive outcome, as well as in the local and systemic consequences of periodontal disease. Fever-range temperatures can induce the expression of heat shock proteins, and the final chapter in the book examines the influence of fever-range hyperthermia on a variety of cells and the organization of plasma membranes. This book is an essential read for graduates and postgraduates in Biology, pro- and eukaryotic Biochemistry, Immunology, Microbiology, Inflammatory and Infectious Disease, and Pathology.
Book Synopsis Fenner and White's Medical Virology by : Christopher J. Burrell
Download or read book Fenner and White's Medical Virology written by Christopher J. Burrell and published by Academic Press. This book was released on 2016-11-09 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fenner and White's Medical Virology, Fifth Edition provides an integrated view of related sciences, from cell biology, to medical epidemiology and human social behavior. The perspective represented by this book, that of medical virology as an infectious disease science, is meant to provide a starting point, an anchor, for those who must relate the subject to clinical practice, public health practice, scholarly research, and other endeavors. The book presents detailed exposition on the properties of viruses, how viruses replicate, and how viruses cause disease. These chapters are then followed by an overview of the principles of diagnosis, epidemiology, and how virus infections can be controlled. The first section concludes with a discussion on emergence and attempts to predict the next major public health challenges. These form a guide for delving into the specific diseases of interest to the reader as described in Part II. This lucid and concise, yet comprehensive, text is admirably suited to the needs of not only advanced students of science and medicine, but also postgraduate students, teachers, and research workers in all areas of virology. Features updated and expanded coverage of pathogenesis and immunity Contains the latest laboratory diagnostic methods Provides insights into clinical features of human viral disease, vaccines, chemotherapy, epidemiology, and control
Book Synopsis Pandemic Outbreaks in the 21st Century by : Buddolla Viswanath
Download or read book Pandemic Outbreaks in the 21st Century written by Buddolla Viswanath and published by Elsevier. This book was released on 2021-08-24 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the past two decades, several pandemics have ravaged the globe, giving us several lessons on infectious disease epidemiology, the importance of initial detection and characterization of outbreak viruses, the importance of viral epidemic prevention steps, and the importance of modern vaccines. Pandemic Outbreaks in the Twenty-First Century: Epidemiology, Pathogenesis, Prevention, and Treatment summarizes the improvements in the 21st century to overcome / prevent / treat global pandemic with future prospective. Divided into 9 chapters, the book begins with an in-depth introduction to the lessons learned from the first pandemic of the 21st century. It describes the history, present and future in terms of detection, prevention and treatment. Followed by chapters on the outbreak, treatment strategies and clinical management of several infectious diseases like MERS, SARD and COVID 19, Pandemic Outbreaks in the Twenty-First Century: Epidemiology, Pathogenesis, Prevention, and Treatment, presents chapters on immunotherapies and vaccine technologies to combat pandemic outbreak and challenges. The book finishes with a chapter on the current knowledge and technology to control pandemic outbreaks. All are presented in a practical short format, making this volume a valuable resource for very broad academic audience. Provides insight to the lessons learned from past pandemics Gives recommendations, future direction in terms of detection, prevention and treatment of pandemics Guides readers through the status and recent developments of vaccines to overcome or prevent pandemics Shows how to enhance the host innate immunity in infectious diseases Includes a chapter on immunotherapies to combat pandemic outbreaks
