Latency Strategies of Herpesviruses

Transcription

1 Latency Strategies of Herpesviruses

2 Latency Strategies of Herpesviruses Edited by Janos Minarovits National Center for Epidemiology Budapest, Hungary Eva Gonczol National Center for Epidemiology Budapest, Hungary Tibor Valyi-Nagy University of Illinois at Chicago Chicago, Illinois, USA

3 Janos Minarovits Microbiological Research Group National Center for Epidemiology H-1529 Budapest Hungary Eva Gonczol Department of Virology National Center for Epidemiology H-1097 Budapest Hungary Tibor Valyi-Nagy Department of Pathology College of Medicine University of Illinois at Chicago Chicago, IL USA Library of Congress Control Number: ISBN-10: X e-isbn-10: ISBN-13: e-isbn-13: Printed on acid-free paper Springer Science+Business Media, LLC All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights springer.com

4 Preface Latency is a most remarkable property of herpesviruses that ensures the maintenance of their genetic information in their hosts for an extended period in the absence of productive replication. Members of all three herpesvirus subfamilies infecting a wide variety of target cells are able to establish latent infection, which is associated with a restricted expression of the viral genome. Latency-associated transcription is either confined to protein noncoding RNAs and/or protein coding RNAs not translated in the latently infected cells or may include transcripts for viral oncoproteins that alter host cell behavior (immortalization, malignant transformation, tumorigenesis). In this book, we wished to review the intriguing latency strategies developed during the estimated 200-million-years-long coevolution (McGeoch and Davison, 1999) of Alpha-, Beta-, and Gammaherpesvirinae and their host species. We put the main emphasis on herpesviruses infecting humans, but we discuss relevant cases of herpesviruses infecting animals as well. We wished to highlight immune evasion tactics used by these viruses as well as the molecular mechanisms regulating the latent promoters of their genomes and signals and molecular pathways resulting in reactivation of latent viral genomes. We gave special attention to epigenetic mechanisms (DNA methylation, histone modifications, chromatin structure) involved in cell-type-specific expression of growth transformation associated gammaherpesvirus genes. The goal of this book is to bring together recent results of herpesvirus research with special attention to latent infections. Although the chapters follow the classical scheme with three subfamilies (Alpha-, Beta-, and Gammaherpesvirinae), we also included special chapters dealing with important aspects of herpesvirus latency, like the modulation of apoptotic pathways and the maintenance of latent, episomal DNA genomes. In the first chapter, Tibor Valyi-Nagy, Deepak Shukla, Herbert H. Engelhard, Jerry Kavouras, and Perry Scanlan describe how alphaherpesviruses (herpes simplex virus and varicella-zoster virus) hide in neurons, giving utmost care to the mechanisms of immune evasion and the molecular biological background (including an epigenetic regulatory mechanism, histone modification) ensuring the almost complete transcriptional silence of the latent genomes. Next, in a special chapter, Klára Megyeri gives a detailed picture of apoptotic pathways modulated by herpes simplex viruses. In the third chapter, Katalin Burian and Eva Gonczol deal with the latency strategies of human cytomegalovirus (HCMV, a betaherpesvirus) discussing the models of differentiation-dependent expression of lytic viral genes and the molecular mechanisms v

5 vi Preface preventing virus production in undifferentiated cells. They give a detailed overview of how HCMV evades innate and adaptive immune responses, too. In Chapter 4, Béla Taródi summarizes the current knowledge on human herpesvirus 6 and 7 latency, highlighting the unique features of the latency-associated transcripts. He pinpoints that one of these betaherpesviruses, HHV-6, can be transmitted in infrequent cases via the germline. In addition to viruses of medical interest, certain herpesviruses infecting animals are also described in this book. In Chapter 5, Julius Rajčáni and Marcela Kúdelová give a detailed description of murid herpesvirus 4, which provides an important animal model for human gammaherpesvirus research. Much less knowledge has accumulated on equine alpha- and gammaherpesviruses: Laszlo Egyed compares the available data on their latency in Chapter 6. Turning to human gammaherpesviruses, Christopher M. Collins and Peter G. Medveczky focus on LANA1 (latencyassociated nuclear antigen 1), a multifunctional nuclear antigen of Kaposi s sarcoma associated herpesvirus (Chapter 7). This sequence-specific DNA binding protein plays a crucial role in the replication and maintenance of the latent, episomal viral genomes and mediates their segregation during cell division. It is also involved in the alteration of cellular behavior (malignant transformation). The properties of LANA1 homologues encoded by Herpesvirus saimiri and murine gammaherpesvirus 68 are also discussed here. In the final chapter, Hans Helmut Niller, Hans Wolf, and Janos Minarovits review the latency strategies of Epstein-Barr virus (EBV). EBV, a Lymphocryptovirus, hides in memory B lymphocytes and contributes to the development of a wide variety of neoplasms. They describe how the expression of latent EBV genes is regulated by DNA (CpG) methylation and how the cell-type-specific usage of latency promoters is reflected in cell-type-specific methylation patterns of the viral genomes (epigenotypes). They also discuss how other epigenetic mechanisms (binding of regulatory proteins, histone modifications) leave their marks on the locus control region (LCR) of the latent viral episome, which persists like an independent chromosomal domain. Janos Minarovits, M.D., D.Sc. Eva Gonczol, M.D., D.Sc. Tibor Valyi-Nagy, M.D., Ph.D.

6 Acknowledgments This book is the result of the efforts of numerous authors, and we thank them for their excellent contributions. We are also grateful to Judit Segesdi for her help in arranging the figures and Dr. Hans Helmut Niller and Dr. Daniel Salamon for proofreading the text. Janos Minarovits, M.D., D.Sc. Eva Gonczol, M.D., D.Sc. Tibor Valyi-Nagy, M.D., Ph.D. vii

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8 Contents Preface Acknowledgments Contributors v vii xi Chapter 1: Chapter 2: Latency Strategies of Alphaherpesviruses: Herpes Simplex Virus and Varicella-Zoster Virus Latency in Neurons Tibor Valyi-Nagy, Deepak Shukla, Herbert H. Engelhard, Jerry Kavouras, and Perry Scanlan Modulation of Apoptotic Pathways by Herpes Simplex Viruses Klára Megyeri Chapter 3: Cytomegalovirus Latency Katalin Burian and Eva Gonczol Chapter 4: Human Herpesvirus 6 and Human Herpesvirus Béla Taródi Chapter 5: Murid Herpesvirus 4 (MuHV-4): An Animal Model for Human Gammaherpesvirus Research Julius Rajčáni and Marcela Kúdelová Chapter 6: Latency Strategies of Equine Herpesviruses Laszlo Egyed Chapter 7: The Multifunctional Latency-Associated Nuclear Antigen of Kaposi s Sarcoma-Associated Herpesvirus Christopher M. Collins and Peter G. Medveczky ix

9 x Contents Chapter 8: Epstein-Barr Virus Hans Helmut Niller, Hans Wolf, and Janos Minarovits List of Abbreviations References Index

10 Contributors Katalin Burian Department of Medical Microbiology and Immunology, University of Szeged, H-6721 Szeged, Dom ter 10, Hungary Christopher M. Collins Department of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30329, USA Laszlo Egyed Veterinary Research Institute of the Hungarian Academy of Sciences, H-1143 Budapest, Hungaria krt 21, Hungary Herbert H. Engelhard Department of Pathology, College of Medicine, University of Illinois at Chicago, 1819 West Polk Street, Room 446, Chicago, IL 60612, USA Eva Gonczol Department of Virology, National Center for Epidemiology, H-1097 Budapest, Gyali út 2-6, Hungary Jerry Kavouras Department of Pathology, College of Medicine, University of Illinois at Chicago, 1819 West Polk Street, Room 446, Chicago, IL 60612, USA Marcela Kúdelová Institute of Virology, Slovak Academy of Sciences, Dubravska 9, Bratislava, Slovak Republic Peter G. Medveczky Department of Medical Microbiology and Immunology and H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33548, USA Klára Megyeri Department of Medical Microbiology and Immunology, University of Szeged, H-6721 Szeged, Dom ter 10, Hungary xi

11 xii Contributors Janos Minarovits Microbiological Research Group, National Center for Epidemiology, H-1529 Budapest, Pihenö u. 1, Hungary Hans Helmut Niller Institute for Medical Microbiology and Hygiene, Research Center, University of Regensburg, Landshuter Str. 22, D Regensburg, Germany Julius Rajčáni Institute of Virology, Slovak Academy of Sciences, Dubravska 9, Bratislava, Slovak Republic Perry Scanlan Department of Pathology, College of Medicine, University of Illinois at Chicago, 1819 West Polk Street, Room 446, Chicago, IL 60612, USA Deepak Shukla Department of Pathology, College of Medicine, University of Illinois at Chicago, 1819 West Polk Street, Room 446, Chicago, IL 60612, USA Béla Taródi Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Dom ter 10, Hungary Tibor Valyi-Nagy Department of Pathology, College of Medicine, University of Illinois at Chicago, 1819 West Polk Street, Room 446, Chicago, IL 60612, USA Hans Wolf Institute for Medical Microbiology and Hygiene, Research Center, University of Regensburg, D Regensburg, Germany