CORONA- AND RELATED VIRUSES Current Concepts in Molecular Biology and Pathogenesis ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 375 DIET AND CANCER: Molecular Mechanisms of Interactions Edited under the auspices of the American Institute for Cancer Research Volume 376 GL YCOIMMUNOLOGY Edited by Azita Alavi and John S. Axford Volume 377 TISSUE RENIN-ANGIOTENSIN SYSTEMS: Current Concepts of Local Regulators in Reproductive and Endocrine Organs Edited by Amal K. Mukhopadhyay and Mohan K. Raizada Volume 378 DENDRITIC CELLS IN FUNDAMENTAL AND CLINICAL IMMUNOLOGY, Volume 2 Edited by Jacques Banchereau and Daniel Schmitt Volume 379 SUBTILISIN ENZYMES: Practical Protein Engineering Edited by Richard Bott and Christian Betzel Volume 380 CORONA-AND RELATED VIRUSES: Current Concepts in Molecular Biology and Pathogenesis Edited by Pierre J. Talbot and Gary A. Levy Volume 381 CONTROL OF THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS IN HEAL TH AND DISEASE Edited by C. Tissa Kappagoda and Marc P. Kaufman Volume 382 MOLECULAR AND SUBCELLULAR CARDIOLOGY: Effects of Structure and Function Edited by Samuel Sideman and Rafael Beyar Volume 383 IMMUNOBIOLOGY OF PROTEINS AND PEPTIDES VIII: Manipulation or Modulation of the Immune Response Edited by M. Zouhair Atassi and Garvin S. Bixler, Jr. A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. CORONA- AND RELATED VIRUSES Current Concepts in Molecular Biology and Pathogenesis Edited by Pierre J. Talbot Annand Frappier Institute University ofQuebec Laval, Quebec, Canada and Gary A. Levy The Toronto Hospital University ofToronto Toronto, Ontario, Canada SPRINGER SCIENCE+BUSINESS MEDIA, LLC Llb~~~V of Congr,"" C.t.log1ng-ln-Publ1c.tlon D~t. Cerenl-- an~ rel.tld Vl~uslS curr.nt concepts In .cl.cul.r blolog~ Ind p.thogBnlsls I '~Ited bV Plerre J. T.lbet Ind G,ry ~. Levy. p. CI. -- (Advlnces In e.perl.ent.l .,dlclnB .nd blclogy . v. 3BO) Includes blbllegraphlc.l references ,nd ,nd ••. ISBN 978-1-4613-5775-9 ISBN 978-1-4615-1899-0 (eBook) DOI 10..1007/978-1-4615-1899-0 1. Coron.vlrus lnfectlons--Congr,ssu. 2. Coron,vlruslS- -Congressis. I. Talbet, PI,rre, 1956- 11. Levy, Gary ~. Uz. S,"In. !:A399. C65 1995 616' .OI94--dc20 95-37889 Cl' Proceedlngs of thc S,xth International Symposmm on Corona and Related V,ruscs. held August 27--5cptcmber 1. 1994, In Quebec City. Quebcc. Canada ISßN 978-1-4613-5775-9 0 1995 Springer Seicnce+8usincss Media New York Originally published by Plenum Press, New York in 1995 Softcover reprint ofthe hardcover 1S I edition 1995 10987654321 All nghts reserved No parI of lh,s book may be rcproduced, slored In a retneval system. ur transmllled In any form or by any means. eleetrome. meehamcal, photocopYlng. m,crof,lm,ng. reeordmg, or OthCrwlse, wllhout wTll1cn permissIon from the Pubhsher PREFACE Corona- and related viruses are important human and animal pathogens that also serve as models for other viral-mediated diseases. Interest in these pathogens has grown tremendously since the First International Symposium was held at the Institute of Virology and Immunobiology of the University of Wiirzburg, Germany. The Sixth International Symposium was held in Quebec City from August 27 to September I, 1994, and provided further understanding of the molecular biology, immunology, and pathogenesis of corona-, toro-, and arterivirus infections. Lectures were given on the molecular biology, pathogenesis, immune responses, and development of vaccines. Studies on the pathogenesis of coronavirus infections have been focused mainly on murine coronavirus, and mouse hepatitis virus. Neurotropic strains ofMHV (e.g., JHM, A59) cause a demyelinating disease that has served as an animal model for human multiple sclerosis. Dr. Samuel Dales, of the University of Western Ontario, London, Canada, gave a state-of-the-art lecture on our current under standing of the pathogenesis of JHM-induced disease. Exciting new work with the identification of cellular receptors has proceeded in a number oflaboratories around the world. This has resulted in the identification of the MHV receptor as members of the carcinoembryonic antigen family; the aminopeptidase-N for the 229E for the human coronavirus and porcine transmissible gastroenteritis virus and 9-0-ace tylated neuraminic acid for bovine coronavirus. The counterpart domains on the viruses are now beginning to be identified. Work on coronavirus attachment and penetration is proceed ing and should provide new insights into the molecular mechanisms involved in cell entry. It has become apparent, however, that virus binding to receptor alone is not sufficient for entry of the virus into the cell. Dr. Kathryn Holmes, Uniformed Services of the Health Sciences, Bethesda, USA provided new insights into the binding domains on viral proteins, demonstrating that the presence of cellular receptors is not always sufficient to allow for infection. Dr. Hubert Laude, Institut Nationale de la Recherche Agronomique, Jouy-en-Josas, France, provided a stimulating lecture on the structure and function of the structural and non-structural proteins of coronaviruses. The nonstructural proteins have been recently identified and one of these proteins, sM, has been discovered to be present on the virion. However, at present its function is unknown, but it may act as a channel protein similar to the influenza M2 protein. Dr. Emil Skamene, Montreal General Hospital, Canada, gave an introductory lecture into the genetics and immunobiology of viral host interactions. Although at present the genetic basis for susceptibility and resistance to coronavirus infection is not clearly estab lished, work in this area will provide important new insights into the mechanisms of viral immunopathogenesis. A number of additional lectures provided insights into the role of cellular and humoral immune mechanisms in the resistance and pathogenesis of disease. v vi Preface Dr. Michael Buchmeier from La Jolla, California, USA, provided new information on the role of cytokines in the pathogenesis ofMHV-induced disease. Dr. Willy Spaan from Leiden, The Netherlands, gave a lecture on the common and distinctive features about corona-, toro-, and arteriviruses. The complete genomic sequences of four coronavirus species are now known and further sequence data was provided for porcine transmissible gastroenteritis virus. Dr. Michael Lai from the Departments of Microbiology and Virology at the University of Southern California, USA, provided new important information on the transcription, replication, recombination and engineering of coronavirus genes. A great deal of research activity has proceeded on characterization of the complex of proteins encoded by the 5'-end of the coronavirus genome which is involved in forming the RNA-dependent RNA polymerase complex. The mechanisms of RNA transcription and its regulation in particular, and of discontinuous transcription of subgenomic mRNAs are still not completely understood; however, a number of lectures provided new insights into these areas of research. Dr. Luis Enjuanes of Madrid, Spain, discussed the development of vaccines against corona- and related virus diseases. These groups of viruses are of major economical importance and thus the development of vaccines is a priority. Various biotechnological approaches are now being explored, including the use of transgenic methodology. The meeting was attended by over 140 scientists and was the largest meeting devoted to this topic to date. The book is organized into eight sections covering pathogenesis, immune responses, vaccine development, viral proteins, cellular receptors, characterization of viral replicase, transcription and replication of viral RNA, recombination and mutation of viral RNA. The book includes proceedings of both podium and poster presentations. The organizers of the meeting wish to thank all ofthose individuals who worked tirelessly to make the meeting a great success. We are especially grateful to Nathalie Arbour, Fanny Chagnon, Charmaine Mohamed, Mathilde Yu, Aurelio Bonavia, Robert Fingerote, Laisum Fung, Alain Lamarre and Vannie Salvas. We also wish to thank the members of the Scientific Advisory Committee for their help in preparing the scientific program: Robert Anderson, Lome Babiuk, Samuel Dales, Serge Dea, 1. Brian Derbyshire, Youssef Elazhary, Lucie Lamontagne and Peter Tijssen. We also wish to take the opportunity to acknowledge the financial support of Sandoz Canada, Inc., SmithKline Beecham Animal Health, Multiple Sclerosis Society of Canada, Universite du Quebec, Institut Armand-Frappier, Medical Research Council of Canada, Rhone Merieux, International Union of Microbiological Societies, Connaught Laboratories Ltd., Na tional Multiple Sclerosis Society (USA), Fort Dodge Laboratories, Ministere de I'Education du Quebec, Biochem Therapeutique, Langford Laboratories, Vetrepharm Canada, Inc., Boehringer Mannheim Canada, and Societe de Promotion Economique du Quebec Metropolitain, without which this meeting would have not been possible. During the banquet that was held during the meeting, a special award and a plaque were presented to Professor Samuel Dales, Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada, for his invaluable lifetime scien tific contributions to this field of research. On behalf of all of us, we wish to express to him our appreciation, gratitude, and pride. The VIIth International Symposium on Corona- and Related Viruses will be held in Spain in 1997 and will be hosted by Dr. Luis Enjuanes. Pierre Talbot Gary A. Levy Professor of Virology Professor of Medicine The Virology Research Centre University of Toronto Institut Armand-Frappier Universite du Quebec CONTENTS Pathogenesis 1. Genetic Resistance to Coronavirus Infection: A Review .................... . Ellen Buschman and Emil Skamene 2. Factors Controlling Coronavirus Infections and Disease of the Central Nervous System: A Review .............................. . . . . . . . . . . . . . .. 13 S. Dales 3. Characterization of the S Protein of Enterotropic Murine Coronavirus Strain-Y .. 23 Susan R. Compton and Satoshi Kunita 4. Biological and Molecular Differentiation between Coronaviruses Associated with Neonatal Calf Diarrhoea and Winter Dysentery in Adult Cattle 29 G. Millane, L. Michaud, and S. Dea 5. Molecular Differentiation of Transmissible Gastroenteritis Virus and Porcine Respiratory Coronavirus Strains: Correlation with Antigenicity and Pathogenicity ............................................... " 35 D. J. Jackwood, H. M. Kwon, and L. J. Saif 6. Organ Specific Endothelial Cell Heterogeneity Influences Differential Replication and Cytopathogenecity ofMHV-3 and MHV-4: Implications in Viral Tropism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 43 J. Joseph, R. Kim, K.Siebert, F.D. Lublin, C. Offenbach, and R.L. Knobler vii viii 7. Genomic Regions Associated with Neurotropism Identified in MHV by RNA-RNA Recombination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51 Ehud Lavi, Qian Wang, Susan T. Hingley, and Susan R. Weiss 8. Involvement of Microtubules and the Microtubule-Associated Protein Tau in Trafficking of JHM Virus and Components within Neurons ............ 57 Kishna Kalicharran and Samuel Dales 9. Evolution and Persistence Mechanisms of Mouse Hepatitis Virus ............. 63 Wan Chen and Ralph S. Baric 10. Spread of MHV-JHM from Nasal Cavity to White Matter of Spinal Cord: Transneuronal Movement and Involvement of Astrocytes ............. 73 S. Perlman, N. Sun, and E. M. Barnett 11. In Vitro Interaction of Coronaviruses with Primate and Human Brain Microvascular Endothelial Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 79 G. F. Cabirac, R. S. Murray, 1. B. McLaughlin, D. M. Skolnick, B. Hogue, K. Dorovini-Zis, and P. 1. Didier 12. Treatment of Resistant AlJ Mice with Methylprednisolone (MP) Results in Loss of Resistance to Murine Hepatitis Strain 3 (MHV-3) and Induction of Macrophage Procoagulant Activity (PCA) . . . . . . . . . . . . . . . . . . . . . . . . .. 89 R. J. Fingerote, J. L. Leibowitz, Y. S. Rao, and G. A. Levy 13. Ultrastructural Characteristics and Morphogenesis of Porcine Reproductive and Respiratory Syndrome Virus Propagated in the Highly Permissive MARC-I45 Cell Clone ......................................... 95 S. Dea, N. Sawyer, R. Alain, and R. Athanassious 14. Antigenic and Genomic Variations among Cytopathic and Non-Cytopathic Strains of Bovine Enteric Coronavirus . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 99 S. Dea, 1. Michaud, and R. Rekik 15. Fragmentation and Rearrangement of the Golgi Apparatus during MHV Infection ofL-2 Cells .......................................... 103 Ehud Lavi, Qian Wang, Anna Stieber, Youjun Chen, Susan Weiss, and Nicholas K. Gonatas 16. Severe Combined Immunodeficiency (SCID) Mouse Hepatitis Experimentally Induced with Low Virulence Mouse Hepatitis Virus .................. 105 Koji Uetsuka, Hiroyuki Nakayama, Naoaki Goto, and Kosaku Fujiwara Contents ix 17. Mouse Hepatitis Virus-Specific CD8+ Cytotoxic T Lymphocytes Induce Apoptosis in Their Target Cells .................................. 109 Shinwa Shibata, Shigeru Kyuwa, Kosaku Fujiwara, Yutaka Toyoda, and Naoaki Goto 18. Echocardiographic Changes following Rabbit Coronavirus Infection .......... 113 Lorraine K. Alexander, Bruce W. Keene, and Ralph S. Baric 19. Neuronal Spread of Swine Hemagglutinating Encephalomyelitis Virus (HEV) 67N Strain in 4-Week-Old Rats .................................. 117 N. Hirano, R. Nomura, T. Tawara, K. Ono, and Y. Iwasaki 20. Characterization of Human T Cell Clones Specific for Coronavirus 229E ....... 121 1. S. Spencer, G. P. Cabirac, C. Best, L. McLaughlin, and R. S. Murray 21. Studies on the in Vitro and in Vivo Host Range of Porcine Epidemic Diarrhoea Virus ........................................................ 131 Anna Utiger, Annekathi Frei, Ana Carvajal, and Mathias Ackermann 22. Coronaviruses in Polarized Epithelial Cells ............................... 135 J.w.A. Rossen, C.PJ. Bekker, w.P. Voorhout, M.C. Horzinek, A. Van Der Ende, G.1.A.M. Strous, and PJ.M. Rottier 23. Isolation and Experimental Oral Transmission in Pigs of a Porcine Reproductive and Respiratory Syndrome Virus Isolate ................ 139 R. Magar, Y. Robinson, C. Dubuc, and R. Larochelle Immune Responses 24. The Protective Role of Cytotoxic T Cells and Interferon against Coronavirus Invasion of the Brain ........................................... 145 Ehud Lavi and Qian Wang 25. MHV-3 Induced Prothrombinase Is Encoded by Musfiblp ................... 151 Rebecca L. Parr, Laisum Fung, Jeffrey Reneker, Nancy Myers- Mason, Julian L. Leibowitz, and Gary Levy 26. Demyelination Induced by Murine Coronavirus JHM Infection of Congenitally Immunodeficient Mice ......................................... 159 J. J. Houtman, H. C. Hinze, and J. O. Fleming x 27. Induction of a Protective Immune Response to Murine Coronavirus with Non-Internal Image Anti-Idiotypic Antibodies ...................... 165 Mathilde Yu and Pierre J. Talbot 28. Transcription and Translation ofProinfiammatory Cytokines following JHMV Infection ..................................................... 173 Stephen A. Stohlman Qin Yao, Cornelia C. Bergmann, Stanley M. Tahara Shigeru Kyuwa, and David R. Hinton 29. Pathology ofMHV-A59 Infection in B2 Microglobulin Negative Mice ......... 179 Ehud Lavi, Qian Wang, James Gombold, Robyn Sutherland, Yvonne Paterson, and Susan Weiss 30. Primary Murine Coronavirus Infection in Mice: A Flow Cytometric Analysis ... 183 S. Kyuwa, K. Machii, A. Okumura, and Y. Toyoda 31. Neurovirulence for Rats of the JHMV Variants Escaped From Neutralization with the S I-Specific Monoclonal Antibodies ........................ 185 Fumihiro Taguchi, Hideka Suzuki, Hiromi Takahashi, and Hideyuki Kubo 32. T Cell Immunodeficiency Involved in Pathogenicity of Attenuated MHV3 Mutants ..................................................... 189 L. Lamontagne, C. Page, and J. P. Martin 33. Impairment of Bone Marrow Pre-B and B Cells in MHV3 Chronically-Infected Mice ........................................................ 193 P. Jolicoeur and L. Lamontagne Vaccine Development 34. Development of Protection against Coronavirus Induced Diseases: A Review ... 197 Luis Enjuanes, Cristian Smerdou, Joaquin Castilla, Ines M. Anton, Juan M. Torres, Isabel Sola, Jose Golvano, Jose M. Sanchez, and Belen Pintado 35. Production and Immunogenicity of Multiple Antigenic Peptide (MAP) Constructs Derived from the S 1 Glycoprotein of Infectious Bronchitis Virus (IBV) .................................................. 213 Mark W. Jackwood and Deborah A. Hilt