VIRAL REPLICATION Edited by German Rosas-Acosta Viral Replication http://dx.doi.org/10.5772/3017 Edited by German Rosas-Acosta Contributors Andrés Santos, Jason Chacón, Germán Rosas-Acosta, George Valiakos, Labrini V. Athanasiou, Antonia Touloudi, Vassilis Papatsiros, Vassiliki Spyrou, Liljana Petrovska, Charalambos Billinis, MariaKuttikan Jayalakshmi, Narayanan Kalyanaraman, Ramasamy Pitchappan, S. Chakraborty, B.M. Veeregowda, R. Deb,, B.M. Chandra Naik, Paul J. Hanson, Huifang M. Zhang, Maged Gomaa Hemida, Xin Ye, Ye Qiu, Decheng Yang, Zeinab N. Said, Kouka S. Abdelwahab Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Marina Jozipovic Typesetting InTech Prepress, Novi Sad Cover InTech Design Team First published February, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Viral Replication, Edited by German Rosas-Acosta p. cm. ISBN 978-953-51-1055-2 Contents Preface VII Chapter 1 Influenza A Virus Multiplication and the Cellular SUMOylation System 1 Andrés Santos, Jason Chacón and Germán Rosas-Acosta Chapter 2 West Nile Virus: Basic Principles, Replication Mechanism, Immune Response and Important Genetic Determinants of Virulence 43 George Valiakos, Labrini V. Athanasiou, Antonia Touloudi, Vassilis Papatsiros, Vassiliki Spyrou, Liljana Petrovska and Charalambos Billinis Chapter 3 Hepatitis B Virus Genetic Diversity: Disease Pathogenesis 69 MariaKuttikan Jayalakshmi, Narayanan Kalyanaraman and Ramasamy Pitchappan Chapter 4 An Overview of the Immune Evasion Strategies Adopted by Different Viruses with Special Reference to Classical Swine Fever Virus 83 S. Chakraborty, B.M. Veeregowda, R. Deb, and B.M. Chandra Naik Chapter 5 Viral Replication Strategies: Manipulation of ER Stress Response Pathways and Promotion of IRES-Dependent Translation 103 Paul J. Hanson, Huifang M. Zhang, Maged Gomaa Hemida, Xin Ye, Ye Qiu and Decheng Yang Chapter 6 Antiviral Replication Agents 127 Zeinab N. Said and Kouka S. Abdelwahab Preface This book is the result of the combined effort of an international panel of experts on different areas of virological research. Therefore, rather than presenting an exhaustive review of a very focused virological area, it provides a collection of in-depth reviews broadly related to the mechanisms of viral replication as applied to various viruses of critical relevance for human or animal disease. Specifically, this book contains six different chapters. Chapter one, “Influenza A Virus Multiplication and the Cellular SUMOylation System,” summarizes our current knowledge of the mechanisms governing Influenza A transcription and replication, and provides an in depth review of our current knowledge of the interactions established between the cellular SUMOylation system and influenza virus during infection, indicating how knowledge related to this topic may lead to innovative new therapeutic approaches against influenza. Chapter two, “West Nile Virus: Basic Principles, Replication Mechanism, Immune Response and Important Genetic Determinants of Virulence,” provides a thorough review of our current knowledge of the molecular biology of West Nile Virus, with emphasis on its structure, genome, replication cycle, epidemiology, pathogenesis, and the genetic determinants of viral virulence. Chapter three, “Hepatitis B Virus Genetic Diversity: Disease Pathogenesis,” gives a general overview of the molecular biology of Hepatitis B virus, with particular emphasis on its mechanisms of replication, the role played by the different proteins encoded by the virus during its life cycle, viral genotypes and sub-genotypes, and their link with pathogenesis in the outcome of viral infection. Chapter four, “An Overview of the Immune Evasion Strategies Adopted by Different Viruses With Special Reference to Classical Swine Fever Virus,” presents a brief review of the general mechanisms used by viruses to evade the immune responses of their host, with special emphasis on the mechanisms used by Classical Swine Fever Virus. Chapter five, “Viral Replication Strategies: Manipulation of ER Stress Response Pathways and Promotion of IRES-Dependent Translation,” presents an in-depth review of our current knowledge of ER Stress Response Pathway and how viral VIII Preface infection utilizes this pathway to stimulate cap-independent (IRES-dependent) translation. Furthermore, it provides an overview of the different Internal Ribosomal Entry Sites encoded by viruses, their classification, mechanism of action, and how viruses manipulate the cellular environment to enhance their activity. And chapter six, “Antiviral Replication Agents,” gives a general overview of antiviral chemotherapeutic agents currently licensed for clinical used and their mechanisms of action, with emphasis on the viral processes and components targeted by them. This book is aimed at students, scholars, professors, and investigators who are peripherally related to, or somehow intrigued by, the different areas of virology covered in this book, as well as at those individuals with greater expertise and knowledge in the topics herein presented who may want up-to-date in depth reviews related to such topics. We expect that, in addition to providing excellent reviews in various exciting areas of virological research, this book will also stimulate the type of scientific discussions and ideas that will result in sustained research efforts not only in the specific areas of research covered in this book, but also in other related areas of biomedical research. German Rosas-Acosta, PhD. Border Biomedical Research Center (BBRC), The University of Texas at El Paso (UTEP), Department of Biological Sciences, The University of Texas at El Paso (UTEP), USA [...]... vRNA Altogether, this not only suggests a pro -viral functionality of UAP56 in 18 Viral Replication enhancing vRNA production, but that efficient viral replication exploits multiple functionalities of cellular host factors in a well orchestrated manner 3.4 Cutting and mincing the viral transcripts: Host splicing machinery and influenza viral RNA Splicing of viral mRNA, needed for the production of M2... of their functions, including viral replication However, influenza virus requires access to the cell nucleus for successful transcription and replication of the viral genome Once in the nucleus, the incoming RdRp associated to the vRNPs initiates synthesis of viral mRNA and produces the first round of viral protein synthesis, which leads to the expression of the early viral proteins PB1, PB2, PA, NP,... Nuclear accumulation and 3D structure of the viral RdRp The release of the vRNPs from the infectious viral particle is perhaps the most critical step in the initiation of viral replication This event requires the acidification of the viral particle core for the disruption of the intermolecular interactions shared between the vRNPs and the M1 viral protein [49] The viral complex responsible for the acidification... The viral envelope surrounds a relatively irregular viral nucleocapsid formed by the viral matrix (M1) protein, which in turn surrounds eight viral ribonucleoproteins (vRNPs) that appear to be placed in a well organized cylindrical arrangement [4] Each vRNP is made of a single stranded viral genomic RNA segment covered by numerous copies of the viral nucleoprotein (NP), and a single copy of the viral. .. the viral polymerase to the 5’-end of the vRNA are both required for transcription [75] This finding led to a refined hypothesis in which the viral polymerase binds to the panhandle structure formed between the complementary regions of the vRNA, recognizes the viral promoter, and subsequently elongates viral mRNA transcripts while remaining bound to the 5’-end of the template [75] Because the viral. .. regions still remains unknown ii) Viral proteins involved in the regulation of the viral polymerase: As mentioned above, viral proteins different from those constituting the vRNP complexes can also play an important regulatory role in the function of the viral polymerase To date, the molecular mechanisms underlying the viral polymerase switch from transcription to replication still remain unresolved... inhibitors or point mutations on the 14 Viral Replication transcriptase activity of the RdRp, since under such conditions these assays do not accurately recapitulate the events involved in viral transcription and replication during influenza infections 3 Cellular factors important for viral multiplication The first identification of cellular factors involved in influenza viral infection took place as early... for efficient vRdRp-dependent transcription of the viral genome In a reporter assay, knockdown of the nuclear Splicing Factor Proline-Glutamine Rich (SFPQ/PSF) reduced levels of viral transcription, but had no effect on viral genome replication Moreover, in vitro analysis of viral transcription revealed about a ~5-fold reduction in the fraction of viral polyadenylated (positive sense) transcripts,... machinery to 10 Viral Replication translate its gene products, influenza has developed a mechanism called “cap-snatching” to prime the synthesis of all viral mRNAs [69] According to in vitro reconstitution assays the cap-snatching event seems to be dependent upon binding of the viral polymerase complex on the viral promoter at the 3’-end of vRNA molecules [63, 69-70] This interaction between the viral RdRp... during infection by neutralizing cellular antiviral responses and increasing viral protein synthesis, while decreasing the synthesis of cellular proteins (reviewed by Hale et al [8], Lin et al [9], and Krug et al [10]) The role of neutralizing antiviral defenses has been recently shown to be shared by another viral protein produced by a limited number of viral strains: The so-called PB1-F2 protein, . VIRAL REPLICATION Edited by German Rosas-Acosta Viral Replication http://dx.doi.org/10.5772/3017. [3]. The viral envelope surrounds a relatively irregular viral nucleocapsid formed by the viral matrix (M1) protein, which in turn surrounds eight viral