Molecular Basis of Viral and Microbial Pathogenesis

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2 38. Colloquium der Gesellschaft for 8iologische Chemie April 1987 in Mosbach/8aden Molecular Basis of Viral and Microbial Pathogenesis Edited by R. Rott and W. Goebel With 90 Figures Springer-Verlag Berlin Heidelberg New York London Paris Tokyo

3 Professor Dr. RUDOLF Ron, Institut for Virologie der Universitat, Frankfurter StraBe 107, 6300 GieBen, FRG Professor Dr. WERNER GOEBEL, Institut for Genetik und Mikrobiologie der Universitat, R6ntgenring 11, 8700 WOrzburg, FRG ISBN-13: e-isbn-13: : / This work is subject to copyright. All rights are reserved. whether the whole or part 01 the material is concerned. specifically the rights 01 translation. reprinting. re-use 01 illustrations, recitation. broadcasting, reproduction on microfilms or in other ways. and storage in data banks. Duplication 01 this publication or parts thereol is only permitted under the provisions 01 the German Copyright Law 01 September , in its version 01 June , and a copyrightlee must always be paid. Violations lall under the prosecution act 01 the German Copyright Law. Springer-Verlag Berlin Heidelberg 1988 Softcover reprint of the hardcover 1 st edition 1988 The use 01 registered names, trademarks. etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. 2131/

4 Preface Elucidation of the mechanisms of pathogenesis underlying the diseases caused by viruses and bacteria has fascinated scientists for many years in two ways. Firstly, these pathogenic agents represent relatively simple biological systems for the study of basic biological processes such as replication, gene regulation, genetic variability and host-pathogen interactions. Secondly, process in this field is valuable in a practical sence, since it can help in the control of these diseases. The availability of new genetic and immunological techniques, especially recombinant DNA methods and monoclonal antibody technology, has provided powerful tools for unravelling the genetic, biochemical and immunological basis of viral and microbial pathogenesis. Molecular cloning has allowed the isolation of single genes or groups of genes related to phenotypes which appear to be immunologically important for pathogenesis. The specific elimination of such genes from the complex genomes of the pathogens can now be achieved with similar genetic techniques. These genetic studies have provided additional information on the role played by specific phenotypic traits in pathogenesis, especially when combined with relevant animal model systems. Furthermore, the structural analysis of important virulence factors and surface antigens may allow the prediction of antigenic domains suitable for the development of new vaccines. The 38th Mosbacher Colloquium focuses on the molecular basis of viral and microbial pathogenesis. The virology part begins with the wellstudied plant viroids. The unusual structure of their genome, as well as knowledge about their replication and pathogenicity, are presented. The molecular basis of virus variability, the role of viral glycoproteins as determinants of pathogenicity and the significance of viral genes in defining the host range of influenza virus infections represent further important topics discussed. Other basic problems for the understanding of viral infections are DNA amplification by viruses, the control of viral promoters and bio-pathogenic aspects of persistent infections that impede neurofunctions. Much progress has recently been achieved in understanding the molecular basis of virulence of those bacteria that colonize cell surfaces. In particular, the genes for a large number of bacterial toxins, for specific surface structures involved in adhesion and for antiphagocytic activity have been studied in great detail. Significant contributions are provided here on the genetics of Shiga-like toxin, pertussis toxin, cytolysins as well as tetanus and botulinum toxins. The antigenic variations in Neisseria gonoy'y'hoeae and the molecular architecture of the streptococcal M proteins are exciting examples of the importance of bacterial surface structures in evading the host defense. The recent progress in understanding the mechanisms involved in invasion and survival of intracellular bacteria is exemplified in elegant genetic and biochemical studies on Shigella flexney'i. The final part of this colloquium addresses modern trends in the molecular biology of parasites, the oncology of one-gene-transducing viruses and the important question of how host genes control the susceptibility

5 VI to a virus. The 38th Mosbacher Colloquium thus provides an excellent insight into a fascinating field of modern biochemical and medical research. Acknowledgements The organizers are grateful to the Gesellschaft fur Biologische Chemie and its Chairman Prof. Dr. E.-L. Winnacker for their active support of this colloquium. Special thanks are due to Prof. Dr. H. Gibian and Dr. E. Truscheit and all their co-workers for technical help and to all individuals and institutions, in particular the Deutsche Forschungsgemeinschaft, for providing funds and contributing towards making this colloquium a success. September 1987 R. Rott and W. Goebel

6 Contents Correlation Between Viroid Structure and Pathogenicity H.L. SKnger and B. Haas (With 6 Figures) Antigenicity of the Influenza Haemagglutinin Membrane Glycoprotein J. J. Skehel and D. C. Wiley Viral Glycoproteins as Determinants of Pathogenicity H.-D. Klenk, M. Tashiro, W. Garten, and R. Rott (With 3 Figures) Virus Genes Involved in Host Range and Pathogenicity C. Scholtissek (With 6 Figures) Molecular Heterogeneity of Pathogenic Herpes Viruses M. Mach, H.H. Niller, and B. Fleckenstein (With 6 Figures) 51 Recombination of Foreign (Viral) DNA with the Host Genome Studies in Vivo and in a Cell-Free System W. Doerfler, A. Spies, R. Jessberger, U. Lichtenberg, C. Zock, and T. Rosahl (With 4 Figures) 60 Disorders of Cellular Neuro-Functions by Persistent Viral Infections K. Koschel (With 12 Figures) Pathogenetic Aspects of Measles Virus-Persistent Infections in Man V. ter Meulen Analysis of the Dual Lineage Specificity of E26 Avian Leukemia Virus T. Graf, S. Grieser, and M. Nunn (With 2 Figures). 91 Mx Gene Control of Influenza Virus Susceptibility O. Haller and P. Staeheli (With 5 Figures).. 95 Shiga and Shiga-Like Toxins: A Family of Related Cytotoxins A.D. O'Brien, M.P. Jackson, L.R.M. Marques, N.A. Strockbine, D.L. Weinstein, M.A. Moore, R.K. Holmes, J.W. Newland, and R.J. Neill (With 1 Figure) Molecular Mechanisms of Pathogenicity in ShigeUa!Zexneri P.J. Sansonetti, B. Baudry, P. Clerc, A.T. Maurelli, X. Nassif, and A. Ryter Antigenic Variation of Proteins on the Surface of Pathogenic Neisseriae T.F. Meyer, R. Haas, and A. Stern (With 7 Figures) 114

7 VIII Molecular and Antigenic Architecture of the Antiphagocytic Group A Streptococcal M Protein V.A. Fischetti, K.F. Jones, S. Hollingshead, and J.R. Scott (With 5 Figures) Bacterial Cytolysins that Form Transmembrane Pores S. Bhakdi and J. Tranum-Jensen Bacterial Cytolysins - Extracellular Proteins and Virulence Factors S. Kathariou, J. Hacker, H. Hof, I. Then, W. Wagner, M. Kuhn, and W. Goebel (With 9 Figures) Iron as a Signal in Bacterial Infections V. Braun, E. Fischer, K. Hantke, and H. Rotering (With 6 Figures) Clostridial Neurotoxins - The Search for a Common Mode of Action E. Habermann (With 14 Figures) Stage-Specifically Expressed Antigens and Genes in Trypanosoma cruzi G. Harth, C.G. Haidaris, and M. So (With 4 Figures) 176

8 Contributors You will find the addresses at the beginning of the respective contribution Baudry, B. 109 Marques, L.R.M. 102 Bhakdi, S. 132 Maurelli, A.T. 109 Braun, v. 151 Meyer, T.F. 114 Clerc, P. 109 Moore, M.A. 102 Doerfler, W. 60 Nassif, X 109 Fischer, E. 151 Neill, R.J. 102 Fischetti, V.A. 123 Newland, J. VV'. 102 Fleckenstein, B. 51 Niller, H.H. 51 Garten, W. 25 Nunn, M. 91 Goebel, W. 141 O'Brien, A.D. 102 Graf, T. 91 Rosahl, T. 60 Grieser, S. 91 Rotering, H. 151 Haas, B. 1 Rott, R. 25 Haas, R. 114 Ryter, A. 109 Habermann, E. 160 Sansonetti, P.J. 109 Hacker, J. 141 Sanger, H.L. 1 Haidaris, C.G. 176 Scholtissek, C. 39 Haller, o. 95 Scott, J.R. 123 Hantke, K. 151 Skehel, J.J. 21 Harth, G. 176 So, M. 176 Hof, H. 141 Spies, A. 60 Hollingshead, S. 123 Staeheli, P. 95 Holmes, R.K. 102 Stern, A. 114 Jackson, M.P. 102 Strockbine, N.A. 102 Jessberger, R. 60 Tashiro, M. 25 Jones, K.F. 123 ter Meulen, V. 85 Kathariou, S. 141 Then, I. 141 Klenk, H.-D. 25 Tranum-Jensen, J. 132 Koschel, K. 73 Wagner, W. 141 Kuhn, M. 141 Weinstein, D.L. 102 Lichtenberg, u. 60 Wiley, D.C. 21 Mach, M. 51 Zock, C. 60