Interaction of a Mammalian Virus with Host RNA Silencing Pathways PDF Download

Author: Bradford Michael Stadler
Publisher:
ISBN:
Category :
Languages : en
Pages : 320

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Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
The microRNA (miRNA) and RNA interference (RNAi) pathways have recently emerged as an important aspect of virus-host cell interaction. This interaction can occur in several different ways and may favor either the virus or the host cell. Plants and invertebrates use RNAi as a first line of defense against virus infection by cleaving long, double-stranded viral transcripts into small interfering RNAs. However, it remains to be determined whether mammalian cells also initiate a similar response to infection. Here we present evidence that mammalian cells in fact do not induce an antiviral RNAi defense in response to infection by primate retroviruses. Viruses may also interact with host cells by encoding miRNAs to regulate either cellular or viral gene expression. Here we demonstrate that herpes simplex virus type 1 (HSV-1) encodes at least five miRNAs which are primarily expressed during latency. Two of these miRNAs modulate expression of viral genes required for productive replication. We hypothesize that down regulation of these viral genes by these latency associated miRNAs allows HSV-1 to establish and maintain the latent state.

Author: Poornima Parameswaran
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Small RNAs that are 19-30 nucleotides in length use the genetic information encoded in their sequence to effect gene regulation in a sequence-directed manner. Infections with RNA viruses in plants, worms and flies generate short viral-derived RNAs ("vsRNAs") that map to the genome of the infecting virus. The regulated production of these vsRNAs and their engagement by the immune apparatus is essential for inhibiting viral growth, making vsRNAs important components of antiviral immunity in these organisms. RNA virus-derived vsRNA-mediated gene silencing is yet to be demonstrated in mammalian systems. We investigated diverse RNA virus-mammalian systems, and characterized changes in small RNA populations that occur during viral infection in animal cells using high-throughput sequencing. Due to the large number of samples to be analyzed, we designed DNA barcodes to 'tag' RNA samples from individual experiments, which facilitated sequencing in parallel from multiple samples. Our work demonstrated the generality of RNA virus-derived vsRNA production, and the ability of the cellular short RNA apparatus to engage these vsRNAs in worms during Flock House Virus replication, and in mammalian cells during infections with Hepatitis C, Polio, Dengue, Vesicular Stomatitis or West Nile virus. In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host-encoded small RNA (miRNA) profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We found evidence for populations of vsRNAs that exist as duplexed small interfering RNAs ("siRNAs; " effectors of gene silencing) with zero to three nucleotide 3' overhangs. We also observed strand-selective loading of siRNAs onto Argonaute complexes, which are mediators of gene silencing. We quantitated the capacity of these HCVrep-derived vsRNAs to down-regulate target mRNAs in a sequence-specific manner in mammalian systems. We found that abundant HCVrep vsRNAs are not capable of mediating robust silencing (i.e. 2-fold or higher) of Luciferase reporters that have been engineered with vsRNA targets. Additionally, over-expression of siRNAs corresponding to five abundant vsRNAs failed to enhance silencing of Hepatitis C Virus mRNA. These results complement each other and suggest that in mammalian hosts, the virus may coexist with an abundant population of vsRNAs. Questions still remain as to whether robust gene silencing may be achieved by the cooperative action of abundant vsRNAs, or if abundant vsRNAs specifically inhibited from functioning in gene silencing, or alternatively, if they have novel roles in pathways distinct from gene silencing.

Author: Ronald P. van Rij
Publisher: Humana Press
ISBN: 9781617790362
Category : Medical
Languages : en
Pages : 0

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Book Description
Viruses and RNAi share an intricate relationship at many levels. RNAi is an important antiviral defense mechanism in plants and invertebrates, microRNAs – of viral or cellular origin – affect many aspects of virus biology, and replication of many, if not all, mammalian viruses can be suppressed by RNAi. Antiviral RNAi: Concepts, Methods, and Applications provides a collection of protocols for the analysis of viral small RNAs and natural antiviral RNAi responses as well as for the development and optimization of RNAi-based antiviral drugs. As RNAi is a central regulatory mechanism in the cell, the methods in this volume can also be applied out of the context of a virus infection. Divided into five convenient parts, this detailed volume reviews important basic concepts in the field of antiviral RNAi, provides experimental and bio-informatic tools for the analysis of small silencing RNAs, covers methods to biochemically dissect RNAi-based antiviral defense and viral counter-defense mechanisms, describes methods for the design, expression, and delivery of therapeutic antiviral siRNAs, and finally presents genome-wide RNAi approaches for the identification of factors involved in virus replication. Written in the highly successful Methods in Molecular BiologyTM series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Antiviral RNAi: Concepts, Methods, and Applications serves as an ideal guide for both novice and experienced researchers alike striving to dissect the role of RNAi in the viral life cycle or to further boost the development of novel therapeutics and experimental tools based on RNAi technology.

Author: Jennifer Lin Umbach
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :

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Book Description
The microRNA (miRNA) and RNA interference (RNAi) pathways have recently emerged as an important aspect of virus-host cell interaction. This interaction can occur in several different ways and may favor either the virus or the host cell. Plants and invertebrates use RNAi as a first line of defense against virus infection by cleaving long, double-stranded viral transcripts into small interfering RNAs. However, it remains to be determined whether mammalian cells also initiate a similar response to infection. Here we present evidence that mammalian cells in fact do not induce an antiviral RNAi defense in response to infection by primate retroviruses. Viruses may also interact with host cells by encoding miRNAs to regulate either cellular or viral gene expression. Here we demonstrate that herpes simplex virus type 1 (HSV-1) encodes at least five miRNAs which are primarily expressed during latency. Two of these miRNAs modulate expression of viral genes required for productive replication. We hypothesize that down regulation of these viral genes by these latency associated miRNAs allows HSV-1 to establish and maintain the latent state.

Author: Alfonso J. Rodriguez-Morales
Publisher: BoD – Books on Demand
ISBN: 1789848245
Category : Medical
Languages : en
Pages : 179

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Book Description
Tropical emerging diseases pose a significant risk for the circulation of old and new pathogens in areas previously unknown, also implying the possibility of new morbidities and mortalities and new consequences for naïve populations. Globalization, migration and travel are key factors for tropical diseases, and represent the need for integration of tropical medicine, travel medicine and epidemiology in the understanding of such complex situations. Neglected tropical diseases such as leprosy or Chagas disease, arboviral diseases, HIV, Ebola, and arenaviral infections are just a few examples. This book tries to update significant epidemiological and clinical research in many aspects with a multinational perspective.

Author: Yuri Dyakov
Publisher: Elsevier
ISBN: 0080469337
Category : Science
Languages : en
Pages : 497

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Book Description
This book offers a collection of information on successive steps of molecular ‘dialogue’ between plants and pathogens. It additionally presents data that reflects intrinsic logic of plant-parasite interactions. New findings discussed include: host and non-host resistance, specific and nonspecific elicitors, elicitors and suppressors, and plant and animal immunity. This book enables the reader to understand how to promote or prevent disease development, and allows them to systematize their own ideas of plant-pathogen interactions. * Offers a more extensive scope of the problem as compared to other books in the market* Presents data to allow consideration of host-parasite relationships in dynamics and reveals interrelations between pathogenicity and resistance factors* Discusses beneficial plant-microbe interactions and practical aspects of molecular investigations of plant-parasite relationships* Compares historical study of common and specific features of plant immunity with animal immunity

Author: M.A. Matzke
Publisher: Springer Science & Business Media
ISBN: 9401141835
Category : Science
Languages : en
Pages : 297

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Book Description
This book is an up-to-date and comprehensive collection of reviews on various aspects of epigenetic gene silencing in plants. Research on this topic has undergone explosive growth during the past decade and has revealed novel features of gene regulation and plant defense responses that also apply to animals and fungi. Gene silencing is relevant for agricultural biotechnology because stable expression of transgenes is required for the successful commercialization of genetically engineered crops. The reviews have been written by distinguished authors who have made significant contributions to plant gene silencing research. This volume supersedes other books on gene silencing by focussing on plant systems, where many pioneering experiments have been performed, and by including the latest developments from top laboratories. The book is geared toward advanced students of genetics and plant sciences as well as applied and basic research scientists who work with transgenic organisms and epigenetic regulation of gene expression.

Author: Esteban Domingo
Publisher: Academic Press
ISBN: 0128163321
Category : Science
Languages : en
Pages : 426

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Book Description
Virus as Composition, Complexity, Quasispecies, Dynamics, and Biological Implications, Second Edition, explains the fundamental concepts surrounding viruses as complex populations during replication in infected hosts. Fundamental phenomena in virus behavior, such as adaptation to changing environments, capacity to produce disease, and the probability to be transmitted or respond to treatment all depend on virus population numbers. Concepts such as quasispecies dynamics, mutations rates, viral fitness, the effect of bottleneck events, population numbers in virus transmission and disease emergence, and new antiviral strategies are included. The book's main concepts are framed by recent observations on general virus diversity derived from metagenomic studies and current views on the origin and role of viruses in the evolution of the biosphere. Features current views on key steps in the origin of life and origins of viruses Includes examples relating ancestral features of viruses with their current adaptive capacity Explains complex phenomena in an organized and coherent fashion that is easy to comprehend and enjoyable to read Considers quasispecies as a framework to understand virus adaptability and disease processes

Author: R. E. F. Matthews
Publisher: Academic Press
ISBN: 1483258661
Category : Technology & Engineering
Languages : en
Pages : 916

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Book Description
Plant Virology, Second Edition, was written to cover the substantial developments in many areas of plant virology since the first edition was published. Advances have been made in all branches of the subject, but these have been most far reaching with respect to the structure of viruses and of their components, and in the understanding of how viral genomes are organized and how viruses replicate in cells. Significant developments have also occurred in the understanding of how viruses are transmitted by invertebrates and in the application of control measures for specific diseases. The taxonomy of viruses has advanced significantly, and there are now 25 internationally approved families and groups of plant viruses. All these developments have required that most sections be entirely rewritten. This book is intended primarily for graduate students in plant pathology, plant virology, general virology, and microbiology, and for teachers and research workers in these fields. It should also prove useful to some people in related disciplines—molecular biologists, biochemists, plant physiologists, and entomologists.