Biology and Pathogenesis of Rhabdo- and Filoviruses

Biology and Pathogenesis of Rhabdo- and Filoviruses

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Biology and Pathogenesis of Rhabdo- and Filoviruses Editors Asit K Pattnaik University of Nebraska-Lincoln, USA Michael A Whitt University of Tennessee Health Science Center, USA World Scientific NEW JERSEY LONDON SINGAPORE BEIJING SHANGHAI HONG KONG TAIPEI CHENNAI

Published by World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore 596224 USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE Library of Congress Cataloging-in-Publication Data Biology and pathogenesis of rhabdo- and filoviruses / editors, Asit K. Pattnaik, Michael A. Whitt. p. ; cm. Includes bibliographical references and index. ISBN 978-9814635332 (hardback : alk. paper) I. Pattnaik, Asit Kumar, editor. II. Whitt, Michael A., editor. [DNLM: 1. Rhabdoviridae--physiology. 2. Filoviridae--pathogenicity. 3. Filoviridae--physiology. 4. Rhabdoviridae--pathogenicity. QW 168.5.R2] QR415 579.2'566--dc23 2014042992 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Copyright 2015 by World Scientific Publishing Co. Pte. Ltd. All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the publisher. For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher. Cover Illustration: (Left) Scanning electron micrograph of a BHK-21 cell infected with a mutant VSV (Y to A substitution in the PPPY motif of the viral M protein) showing a majority of virus particles tethered to the plasma membrane due to a defect in virus release. The background is pseudo-colored purple, the cell surface is tan and virions are yellow. Image provided by Gopal Murti, Ph.D., Retired Director of Scientific Imaging in St. Jude Children s Research Hospital and Adjunct Professor of Pathology at The University of Tennessee Health Science Center. (Right) Scanning electron micrograph of Ebola virus shedding from the surface of a Vero (African green monkey kidney epithelial) cell. Image provided by Dr. Hideki Ebihara, Ms. Elizabeth Fischer, and Ms. Anita Mora of Rocky Mountain Labs/NIAID/NIH. Printed in Singapore

FOREWORD With the emergence of new viruses and the most devastating outbreak of Ebolavirus ever recorded currently ongoing, this book provides a timely, up-to-date and comprehensive review of the many intriguing aspects of rhabdoviruses and filoviruses. Among these viruses are important pathogens that remain a scourge to the human race, such as rabies, Marburg, and Ebola viruses. Other members of these groups, notably vesicular stomatitis virus (VSV), proved to be extremely valuable models that provided a wealth of information on the structure and replication of negative-strand RNA viruses, in general, and other enveloped viruses. Understanding the biology and molecular basis of the pathogenesis of some these viruses have been long-standing interests of our own laboratories and it is exciting to see a compendium of topics in this book covering the most recent advances. The major focus of the early research on VSV centered on gleaning knowledge of the unique bullet-shaped morphology of VSV and the nature of defective interfering particles and their roles in pathogenesis and replication of VSV. A breakthrough in VSV research occurred in 1970, when Baltimore, Huang, and Stampfer demonstrated that the virus particle contains an RNA-dependent RNA polymerase that transcribes the negative-strand genomic RNA in vitro into RNA products complementary to genomic RNA. This discovery led to a flurry of research on other non-segmented, negative-strand (NNS) RNA viruses. VSV showed robust growth in cultured cells, could be purified in large quantities, and elicited significant in vitro transcription activity. Therefore, VSV quickly became a leading prototype virus for studying this group of viruses. Subsequent work on VSV through genetic manipulation of the viral genome as well as expression and characterization of the viral proteins systematically unfolded the pathways leading to the transcription and replication of its genomic RNA v

vi Biology and Pathogenesis of Rhabdo- and Filoviruses and helped facilitate our understanding of similar processes in other NNS RNA viruses, as detailed in this book. Discovery of a unique mrna capping mechanism in VSV, and possibly in other NNS RNA viruses, offers a unique opportunity for drug development against these pathogens. Tremendous progress has also been made in recent years in the area of structural biology providing an understanding of the overall structure of the virions and deeper insight into structure-function relationships with regard to the fusion activity of the G protein and the transcriptive functions of the ribonucleoprotein complex. The viral genomes have been creatively exploited to insert foreign genes within the intergenic regions. Such recombinant vectors have been effectively used to develop vaccines and to explore the oncolytic potential of the recombinant viruses. When Marburgvirus was discovered in 1967, it was clear that it morphologically resembled rhabdoviruses. This led to the initial proposal to classify Marburgvirus and its younger companion Ebolavirus in the Rhabdoviridae family, and it took some time until the Filoviridae was established in 1982 as a separate family. Not surprisingly, molecular studies on filoviruses followed the paths paved by the pioneering research on rhabdoviruses, particularly VSV, showing that the structural principles and the replicative mechanisms were similar in both virus groups. As with the rhabdoviruses, the use of reverse genetics systems for filoviruses led to greater understanding of many aspects of virus replication mechanisms, functions of viral proteins and host cell responses to viral infections. Since work on these highly pathogenic viruses require the highest level of biocontainment facility, innovative approaches including minigenome systems and viruses having less than the full complement of the viral genome could be used in lower containment facilities to screen for drugs against these dreaded pathogens. Such approaches as well as the use of wild-type viruses in animal models have led to the identification of several experimental drugs that are likely to have significant impact in controlling infections and disease outcomes. We are currently witnessing the most devastating and unprecedented Ebolavirus outbreak on record. In the past, filoviruses re-emerged

Foreword vii periodically, and most of the outbreaks were confined to remote areas of Central Africa and never involved more than 500 cases. Barrier nursing and other classical hygiene practices, such as simple quarantine of patients, have stopped all of these previous outbreaks. The present one is different. Since the first cases were observed in February 2014 in forested areas of South Western Guinea, it has grown steadily in terms of infected people and geographic spread. Besides Guinea, large parts and densely populated urban areas of neighboring countries are now disease ridden. As of early October 2014, more than 8000 cases and 3800 deaths, including many victims among health care workers and physicians, have been reported. The damage to the economy of the affected countries is enormous already, and an end of the epidemic is not in sight. FDA approved medicines and vaccines against Ebolavirus are not available, but experimental treatments have been around for more than a decade as described in detail in this book. Antibody cocktails, sirna-based antivirals, as well as vaccines based on recombinant VSV and other viruses have shown enormous promise in experimental animal models. It is urgent that these drugs are now developed from the experimental stage to clinical application. Information on pathogenesis, immune evasion, evolution, and epidemiology of filoviruses may also help to control this outbreak. Several chapters in this book provide excellent analyses of these and many other topics as well as a grand panorama of the entire field. This is exactly what is needed in the present situation. The book therefore, could not be more timely. Amiya K. Banerjee, Ph.D., D.Sc. Department of Molecular Genetics Lerner Research Institute Cleveland Clinic Cleveland, Ohio 44195, USA Hans Dieter Klenk, M.D. Institut für Virologie Philipps-University Marburg 35043 Germany

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CONTENTS Foreword 1. Overview of Rhabdo- and Filoviruses 1 Asit K. Pattnaik and Michael A. Whitt 2. Rhabdovirus Structure 15 Ming Luo 3. The Pathway of VSV Entry into Cells 33 Shem Johnson and Jean Gruenberg 4. Rhabdovirus Glycoproteins 49 Yves Gaudin and Michael A. Whitt 5. VSV RNA Transcription and Replication 75 Jacques Perrault 6. Host Cell Functions in Vesicular Stomatitis 107 Virus Replication Phat X. Dinh, Anshuman Das, and Asit K. Pattnaik 7. Cytopathogenesis of Rhabdoviruses 141 Douglas S. Lyles 8. Assembly and Budding of Rhabdo- and Filoviruses 171 Ziying Han and Ronald N. Harty 9. Rhabdoviruses as Vaccine Vectors: From Initial 199 Development to Clinical Trials John K. Rose and David K. Clarke v 10. Oncolytic Rhabdoviruses 231 Nicole E. Forbes and John C. Bell ix

x Biology and Pathogenesis of Rhabdo- and Filoviruses 11. Use of Rhabdoviruses to Study Neural Circuitry 263 Melanie Ginger, Guillaume Bony, Matthias Haberl, and Andreas Frick 12. Evolution of Rhabdo- and Filoviruses 289 Isabel S. Novella, John B. Presloid, and R. Travis Taylor 13. Emerging Rhabdoviruses 311 Imke Steffen and Graham Simmons 14. Rabies Virus Replication and Pathogenesis 335 Andrew W. Hudacek and Matthias J. Schnell 15. Activation and Evasion of Innate Immune 353 Response by Rhabdoviruses Karl-Klaus Conzelmann 16. Rabies Virus Vaccines 387 Ying Huang, Clement W. Gnanadurai, and Zhen F. Fu 17. Filovirus Structure and Morphogenesis 427 Timothy F. Booth, Daniel R. Beniac, Melissa J. Rabb, and Lindsey L. Lamboo 18. Epidemiology and Pathogenesis of Filovirus Infections 453 Logan Banadyga and Hideki Ebihara 19. Filovirus Entry into Susceptible Cells 487 Rohit K. Jangra, Eva Mittler, and Kartik Chandran 20. Filovirus Transcription & Replication 515 Kristina Brauburger, Laure R. Deflubé, and Elke Muhlberger 21. Innate Immune Evasion Mechanisms of Filoviruses 557 Christopher F. Basler, Gaya K. Amarasinghe, and Daisy W. Leung 22. Vaccines and Antivirals for Filoviruses 587 Chad E. Mire & Thomas W. Geisbert Index 621