MOLECULAR BIOLOGY AND PATHOGENESIS OF CORONA VIRUSES

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY

Editorial Board:

NATHAN BACK, State University of New York at Buffalo

NICHOLAS R. DI LUZIO, Tulane University School of Medicine

EPHRAIM KATCHALSKI-KATZIR, The Weizmann Institute of Science

DAVID KRITCHEVSKY, Wistar Institute

ABEL LAJTHA, Rockland Research Institute

RODOLFO PAOLETTI, University of Milan

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Volume 173 MOLECULAR BIOLOGY AND PATHOGENESIS OF CORONAVIRUSES

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MOLECULAR BIOLOGY AND PATHOGENESIS OF CORONAVIRUSES

Editedhy

P. J. M. Rottier B. A. M. van der Zeijst w. 1. M. Spaan and

M. C. Horzinek State University of Utrecht Utrecht, The Netherlands

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

EMBO Workshop on Molecular Biology and Pathogenesis of Coronaviruses (1983: State University of Utrecht) Molecular biology and pathogenesis of coronaviruses.

(Advances in experimental medicine and biology; v. 173) "Proceedings of an EMBO Workshop on Molecular Biology and Pathogenesis of

Coronaviruses, held June 1983 at the State University of Utrecht, The Netherlands." - T.p. verso.

Includes bibliographical references and index. 1. Coronaviruses-Congresses. 2. Virus disease-Congresses. 3. Molecular biology­

Congresses. I. Rottier, P. J. M. II. Title. III. Series. [DNLM: 1. Coronaviridae­Congresses. 2. Coronavirus infections-Etiology-Congresses. WI AD559 v.173/QW 168.5.C8 E53m 1983] QR399.E43 1983 636.089'60194 84-4710

Proceedings of an EMBO Workshop on Molecular Biology and Pathogenesis of Coronaviruses, held June 1983 at the State University of Utrecht, The Netherlands

©1984 Plenum Press, New York Softcover reprint of the hardcover 18t edition 1984

A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013

All rights reserved

No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

ISBN-13: 978-1-4615-9375-1 e-ISBN-13: 978-1-4615-9373-7 DOl: 10.10071 978-1-4615-9373-7

PREFACE

The present volume contains the Proceedings of an EMBO Workshop organized in June 1983 by the Institute of Virology, Veterinary Faculty, State University of Utrecht, The Netherlands. Some 70 scientists from 11 countries followed the invitation to present and discuss their recent data on the structure, replication, genetics and pathogenesis of coronaviruses. It was the second international meeting on these viruses; the Workshop, which was held in Zeist near Utrecht followed the example of the Wuerzburg symposium of October 1980.

At that time it became clear that coronaviruses are unique in many respects. Once a group of viruses that were defined merely on the basis of their characteristic peplomer morphology, Coronaviridae family members are known today

- to be constructed from essentially three polypeptides - to use a "nested set" of 5-6 subgenomic mRNAs in the expression

of their large, positive and single stranded RNA genome, - to generate these subgenomic RNAs through specific fusion of non­

contiguous sequences, - to mature by budding from intracellular membranes, - to cause persistent infection with neurological involvement and

sometimes immunopathological conditons.

These and many other findings have been established only very recently. The articles collected in this book reveal and/or further detail these findings. Since these Proceedings contain the combined scientific presentations of representatives from virtually all laboratories engaged in the field, they provide a fairly comprehensive review of the state of the art in corona­virology.

The contents have been grouped into two main parts. The first part deals with the molecular biology of coronaviruses and contains contributions on viral proteins, virus maturation and on the structure and replication of viral RNAs. In the second part

v

vi PREFACE

aspects of coronavirus pathogenesis are described including studies on genetic and immunological factors involved and on persistent infections in tissue culture. Both parts are preceded by synoptic papers compiled by B.W.J.Mahy and V. ter Meulen, respectively.

P.J.M.Rottier B.A.M.van der Zeijst W.J.M.Spaan M.C.Horzinek

CONTENTS

MOLECULAR BIOLOGY OF CORONAVIRUSES

OVERVIEW

Biochemistry of Coronaviruses 1983......................... 1 Brian W.J. Mahy

VIRAL PROTEINS AND MATURATION

Organization of the IBV Genome ••••••••••..•••••••••••••••. 11 David F. Stern and Bartholomew Sefton

Proteolytic Cleavage of the Peplomeric Glycoprotein E2 of MHV Yields Two 90K Subunits and Activates Cell Fusion

Lawrence S. Sturman and Kathryn V. Holmes

25

Coronavirus Maturation ...•..•.•.•.•...•••..••••..•...••.•• 37 Kathryn V. Holmes, Mark F. Frana,

Susan G. Robbins, and Lawrence S. Sturman

In Vitro Assembly of the Murine -----COronavirus Membrane Protein E1

Peter Rottier, Dorothe"e Brandenburg, John Armstrong, Ben van der Zeijst, and Graham Warren

Characterization of Viral Proteins Synthesized in 229E Infected Cells and Effect(s) of Inhibition of Glycosylation and Glycoprotein

S3

Transport .................................................................................. 65 M~C. Kemp, J.C. Hierholzer, A.

Harrison, and J.S. Burks

vii

viii

Defective Replication of Porcine Transmissible Gastroenteritis Virus in a Continuous Cell Line

D.J. Garwes, Lynne Bountiff, G.C. Millson, and Carole J. Elleman

Structural Characterization of IBV

CONTENTS

79

Glycoproteins........................................ 95 David Cavanagh

Use of Monoclonal Antibodies to Assess Antigenic Relationships of Avian Infectious Bronchitis Virus Sero-types in the United States........................... 109

D.B. Snyder and W.W. Marquardt

Monoclonal Antibodies to the Classes of Mouse Hepatitis

Three Virus

Strain A59 Proteins.................................. 115 Marck J.M.Koolen, Albert D.M.E.

Osterhaus, Kees H.J. Siebelink, Marian C. Horzinek, and Bernard A.M. van der Zeijst

Antigenic and Polypeptide Structure of Bovine Enteric Coronavirus as Defined by Monoclonal antibodies..................... 117

J.F. Vautherot, J. Laporte, M.F. Madelaine, P.Bobulesco, and A. Roseto

Plaque Assay, Polypeptide Composition and Immunochemistry of Feline Infectious Peritonitis Virus and Feline Enteric Corona virus Isolates. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . • . . . 133

John F. Boyle, Niels C. James F. Evermann, McKeirnan, Richard L. John W. Black

Pedersen, Alison J. Ott, and

Assembly of 229E Virions in Human Embryonic Lung Fibroblasts and Effects of Inhibition of Glycosylation and Glycoprotein Transport on this Process ••••••••••••••••••••••••••• 149

M.C. Kemp, A. Harrison, J.C. Hierholzer. and J.S. Burks

CONTENTS ix

Amphotericin Inhibits Coronavirus SD, SK and A59 Growth....................................... 151

B.L. DeVald, J.C. Gerdes, J.S. Burks, and M.C. Kemp

Electron Lucent Structures Induced by Coronaviruses........................................ 153

M.C. Kemp, A. Harrison, J.C. Hierholzer, and J.S. Burks

VIRUS SPECIFIC RNAs: STRUCTURE AND REPLICATION

Cloning and Sequencing the Nucleocapsid and El Genes of Coronavirus MHV-A59.................................................. 155

John Armstrong, Sjef Smeekens, Willy Spaan, Peter Rottier, and Ben van der Zeijst

Nucleotide Sequencing of Mouse Hepatitis Virus Strain JHM Messenger RNA 7...................................... 163

Michael Skinner and Stuart Siddell

Transcription Strategy of Coronaviruses: Fusion of Non-Contiguous Sequences During mRNA Synthesis................................ 173

Willy Spaan, Hajo Delius, Mike A. Skinner, John Armstrong, Peter Rottier, Sjef Smeekens, Stuart G. Siddell, and Bernard van der Zeijst

Studies on the Mechanism of RNA Synthesis of a Murine Coronavirus.................... 187

Michael M.C. Lai, Ralph S. Baric, Peter R. Brayton, and Stephen A. Stohlman

Glycoprotein El of MHV-A59: Structure of the O-linked Carbohydrates and Construction of Full Length Recombinant cDNA Clones.............................. 201

Heiner Niemann, Gudrun Heisterberg­Moutsis, Rudolf Geyer, Hans-Dieter Klenk, and Manfred Wirth

DNA Sequencing Clones

Studies of Genomic cDNA of Avian Infectious

Bronchitis Virus..................................... 215 M.E.G. Boursnell. and T.D.K. Brown

x CONTENTS

The Genome of Transmissible Gastroenteritis Virus

Lynne Bountiff, David Geoffry C. Millson, Baird

(TGEV) ............................ . 225 J. Garwes,

and G. David

PATHOGENESIS OF CORONAVIRUSES

OVERVIEW

Biology of Coronaviruses 1983.............................. 227 V. ter Meulen

MHV-A59 Pathogenesis in Mice............................... 237 Ehud Lavi, Donald H. Gilden, Maureen K. Highkin, and Susan R.Weiss

Detection of MHV-A59 RNA by In Situ Hybridization ••••••••••••• ~ •• ~................... 247

Ehud Lavi, Donald H. Gilden, Maureen K. Highkin, and Susan R. Weiss

irological and Immunological Aspects of Corona virus Induced Subacute Demyelinating Encephalomyelitis in Rats. . . . . • . . . . . . . . . . . . . . . . . . . . • . . . . ... • . • • . . . . . • • • • . ... . . 259

H.Wege, R.Watanabe, and V.ter Meulen

A One Year Study of Coronavirus SD Infection in Mice.................................... 271

L.D. Jankovsky, J.S. Burks, P. Licari B.L. DeVald, and M.C. Kemp

Immunosuppression with Cyclophosphamide Does Not Prevent Demyelination or Result in Uncontrolled Viral Replication in Coronavirus SD Infected Mice.............................................. 277

J.S. Burks, Licari, I. T • Kemp

L. Jankovsky, McNally, and

P.A. M.C.

In Vivo and In Vitro Models of Demyelinating Diseases -- VIII: Genetic, Immunologic and Cellular Influences on JHM Virus Infection of Rats .................................................... 279

O. Sorensen, S. Beushausen, S. Puchalski, S. Cheley, R. Anderson, M. Coulter-Mackie. and S. Dales

CONTENTS

Restricted Replication of a Temperature­Sensitive Mutant of MHV-AS9 in

xi

Mouse Brain Astrocytes............................... 299 Mario F. van Berlo, Guus Wolswijk,

Jero Calafat, Marian C. Horzinek, and Ben A.M. van der Zeijst

Replication of Murine Coronaviruses in Somatic Cell Hybrids Formed Between a Mouse Fibroblast Cell Line and either a Rat Schwannoma Line or a Rat Glioma Line ••••••••••••••••••••••••••• 301

Wayne F. Flintoff

Persistent In Vitro Infection with Mouse Hepatitis Virus 3 ••••••••••••••••••••••••••••• 315

Lucie Lamontagne and Jean-Marie Dupuy

Characterization of MHV-AS9 Persistently Infected Cells...................................... 327

Reinald Repp, Teruko Tamura, Hans­Dieter Klenk, and Heiner Niemann

Fine Specificity and Genetic Restriction of T Cell Clones Specific for Mouse Hepatitis Virus, Strain JHM.................... 331

Jerold G. Woodward, John O. Fleming, Glenn K. Mat sushima , Jeffrey A. Frelinger, and Stephen A. Stohlman

The Immune Response to Mouse Hepatitis Virus: Genetic Variation in Antibody Response and Disease..................... 345

Gary A. Levy, Robert Shaw, Julian L. Leibowitz, and Edward Cole

Pathogenic Differences Between Various Feline Coronavirus Isolates ••••••••••••••••••••••••• 365

Niels C. Pedersen, John W. Black, John F. Boyle, James F. Evermann, Alison J. McKeirnan, and Richard L.Ott

Expression of Feline Infectious Peritonitis (FIP) Coronavirus Antigens on the Surface of Feline Macrophage-Like Cells................................ 381

H.E.L. Jacobse-Geels and M.C.Horzinek

d CONTENTS

Role of Circulating Antibodies and Thymus-Dependent Lymphocytes in Production of Effusive Type Feline Infectious Peritonitis after Oral Infection ........................................... 384

Toshiharu Hayashi, Kunio Doi, and Kosaku Fujiwara

Interactions of Porcine Enteric Corona­Virus TGEV with Macrophages and Lymphocytes.......................................... 385

H. Laude, B. Charley, and C. La Bonnardiere

Effect of Stomach and Gut Juices on Infectivity of Low and High Passaged Strains of T.G.E. Coronavirus: Properties of a Virus Mutant Resistant to Inactivation by Stomach Juice Obtained by Cycles of Survivor Selection in Tissue Culture....................................... 387

J.M. Aynaud, E. Bottreau, and A. Brun

Pathogenicity MHV-2cc, Infected

Naoaki Goto, Sato

of Mouse Hepatitis Virus, from a Persistently

DBT Cell Line .•.•.•.•..••.•.•••••..•••.•.•• Norio Hirano, and Akio

The Pathogenesis and Age Related OC43 Virus in Susceptibility of

389

Mice. • . . . . . . . . . . . . . . . . . • . . . . . . . . . • . . . . . . . . . • . . . • . . . . . 391 J. Pearson and C.A. Mims

Failure to Detect Coronavirus SK Antigen in Multiple Sclerosis Brain Tissue by Autoradiography................................... 393

J.S. Burks, B.L. DeVald, J.C. Gerdes, I.T. McNally, and M.C. Kemp

Antiviral Action of Interferon in the Bovine Species: Study In Vitro and In Vivo ••••••••••••••• ::.~................... 395

C. Vanden Broecke, P.P. Pastoret, A. Schwers, A. Goossens, B. Lansival, L. Bugyaki, L. Dagenais, and J. Werenne

CONTENTS

The Effects of Mouse Hepatitis Virus Type 3 on the Microcirculation of

xiii

the Liver in Inbred Strains of Mice.................. 397 G.A. Levy, P.J. MacPhee, L.S. Fung,

M.M. Fisher, and A.M.Rappaport

Contributors ..............................•...•........... 401

Index ..................................................... 405