Arenaviruses: Biology and Immunotherapy

Current Topics in Microbiology 134 and Immunology Editors A Clarke, Parkvi11eNictoria . R W. Compans, Binningham/A labama . M Cooper, Birmingham!A labama H. Eisen, Paris . W. Goebel, Wfuzburg . H. Koprowski, Philadelphia . F. Melchers, Basel . M Oldstone, La Jolla/California . P.K Vogt, Los Angeles H. Wagner, Ulm . 1. Wilson, La Jolla/California This collection of studies was conceived as part of a two volume review of the subject. The contents of Volume 133 are listed below. Arenaviruses: Genes, Proteins, and Expression M.B.A. OLDSTONE: The Arenaviruses - An Introduction D.H.L. BISHOP and D.D. AUPERIN: Arenavirus Gene Struc- ture and Organization P.l. SOUTHERN and D.H.L. BISHOP: Sequence Comparison Among Arenaviruses M.l. BUCHMEIER and B.S. PAREKH: Protein Structure and Expression Among Arenaviruses Y. RIVIERE: Mapping Arenavirus Genes Causing Virulence S.l. FRANCIS, P.l. SOUTHERN, A. VALSAMAKIS, and M.B.A. OLDSTONE: State of Viral Genome and Proteins During Persistent Lymphocytic Choriomeningitis Virus Infection D.H. WALKER and F.A. MURPHY: Pathology and Patho- genesis of Arenavirus Infections Subject Index Arenaviruses Biology and Immunotherapy Edited by M. B. A. Oldstone With 33 Figures Springer-Verlag Berlin Heidelberg NewY ork London Paris Tokyo MICHAEL B.A. OWSTONE, M.D. Department of Immunology Scripps Clinic and Research Foundation 10666 North Torrey Pines Road La Jolla, CA 92037, USA ISBN-13: 978-3-642-71728-4 e-ISBN-13: 978-3-642-71726-0 DOl: 10.1007/978-3-642-71726-0 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprint- ing, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1987 Softcover reprint of the hardcover I st edition 1987 Library of Congress Catalog Card Number 15-12910 The use or 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. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceuti- cal literature Typesetting: Universitatsdruckerei H. Stiirtz AG, Wiirzburg 2123/3130-543210 Table of Contents M.B.A. OLDSTONE: The Arenaviruses- An Introduction . . . . . . . . . 1 e.J. PETERS, P.B. JAHRLING, C.T. Lm, R.H. KENYON, K.T. McKEE JR., and J.G. BARRERA ORO: Experimental Studies of Arenaviral Hemorrhagic Fevers. With 7 Figures . . . . . . . . . . 5 J.B. MCCORMICK: Epidemiology and Control of Lassa Fever. With 1 Figure . . . . . .. .. 69 M.C. WEISSENBACHER, R.P. LAGUENS, and C.E. COTO: Argentine Hemorrhagic Fever. With 1 Figure . . . . . . . . . . . . . . . . 79 C.R. HOWARD: Neutralization of Arenaviruses by Antibody. With 3 Figures . . . . . . . . .. 117 J.E. ALLAN, J.E. DIXON, and P.e. DOHERTY: Nature of the Inflammatory Process in the Central Nervous System of Mice Infected with Lymphocytic Choriomeningitis Virus. With 5 Figures . . . . . . . . . . . . . . . .. . 131 O. MARKER and A.R. THOMSEN: Clearance of Virus by T Lymphocytes Mediating Delayed Type Hypersensitivity. With 6 Figures . . . . . . . . 145 R.M. WELSH: Regulation and Role of Large Granular Lymphocytes in Arenavirus Infections 185 M.B.A. OLDSTONE: Immunotherapy for Virus Infection. With 10 Figures ..... ... 211 S.P. FISHER-HoCH and J.B. MCCORMICK: Pathophysiology and Treatment of Lassa Fever 231 Subject Index 241 Indexed in Current Contents List of Contributors You will find the addresses at the beginning of the respective contribution ALLAN, J.E. 131 Lru, C.T. 5 BARRERA ORO, J.G. 5 MARKER, O. 145 COTO, e.E. 79 MCCORMICK, J.B. 69, 231 DIXON, J.E. 131 McKEE K.T., JR. 5 DOHERTY, P.C. 131 OLDSTONE, M.B.A. 1, 211 FISHER-HoCH, S.P. 231 PETERS, C.J. 5 HOWARD, C.R. 117 THOMSEN, A.R. 145 JAHRLING, P.B. 5 WEISSENBACHER, M.e. 79 KENYON, R.H. 5 WELSH, R.M. 185 LAGUENS, R.P. 79 The Arenaviruses - An Introduction M.B.A. OLDSTONE Viruses are generally studied either because they cause significant human, animal or plant disease or for their utility as materials to probe a basic phenomenon in biology, chemistry, genetics or molecular biology. Arenaviruses are unusually interesting in that they occupy both of these categories. Arenaviruses cause severe human diseases known primarily as the hemor- rhagic fevers occurring in South and Latin America (Bolivia: Machupo virus and Argentina: Junin virus) and in Africa (Lassa virus). Because such viruses produce profound disability and may kill the persons they infect, they are a source of economic hardship in the countries where they are prevalent. Further, they provide new problems for health care personnel owing to the narrowing of the world as visitors from many countries increasingly travel to and from these endemic areas. In addition, lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling than those elicited by other arenaviruses. Yet LCMV is likely of greater concern to non-arena-virologists and experimentalists using tissue culture or animals, i.e., workers in molecular biology, cancer research, virology, immunobiology, etc., because normal appearing cultured cells or tissues and animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and transmit that infection to laboratory workers (reviewed OLDSTONE and PETERS 1978). For example, HINMAN et al. (1975) re- corded 48 cases among personnel in the radiotherapy department and vivarium at the University of Rochester School of Medicine. These persons had contact with Syrian hamsters into which tumors, unknown to be occultly infected with LCMV, were transferred. These tumors were obtained from an outside research supplier who distributed tumor cell lines to numerous laboratories primarily interested in SV -40 and polyoma virus research. In subsequent investigation of the 22 tumor lines in question, 13 yielded infectious LCMV. Infection was spread from the experimental area, presumably via air ducts. Similarly, the Communicable Disease Center, USA, has recorded multiple cases of LCMV infections in families scattered from the northeast coast of the United States (New York) to the western region (Reno, Nevada) originating from hamsters sold by a single supplier in the southeast (Florida). Several investigators found that their hybridomas making monoclonal antibodies were infected with LCMV. The mechanism was likely by the use of infected splenic feeder cells obtained Department of Immunology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA Current Topics in Microbiology and Immunology, Vol. 134 © Springer-Verlag Berlin· Heidelberg 1987 2 M.B.A. Old stone Table 1. Recognized Arenavirus diseases of man Virus Disease Locality Rodent Person to Laboratory reservoir person model of and vector trans- human mission infection Lymphocytic Grippe, aseptic Probably origi- Mus musculus Never Mouse chorio- meningitis, oc- nated in Europe, natural host; documented meningitis casional more now worldwide colonized ro- severe forms dents, parti- of meningoence- cularly mice phalomyelitis and hamster; dog? Junin Argentinian Circumscribed Calomys mus- Occasional Guinea pig hemorrhagic area of Argen- culinus, pos- fever tina; Buenos sibly others Aires to northeast Machupo Bolivian Beni region Calomys Occasional, Rhesus hemorrhagic of Bolivia callosus particularly monkey fever spouses; recog- nized hospital outbreak Lassa Lassa fever Western Africa Mastomys Frequent; Squirrel mon- nataliensis blood con- key, Guinea tamination pig strain 13 LCMVWEin guinea pig from clinically healthy but persistently infected mice purchased from a commer- cial source. Hence, researchers studying such diverse areas as the molecular biology of SV4 0, biologic effects of chlamydia, immune responses of mice mak- ing hybridoma cells or production of ascites fluids have found their preparations contaminated with LCMV (LEHMANN-GRUBE 1973; WHO Bulletin 1975; GRIM- WOOD 1983, 1985; VAN DER ZElJST et al. 1983a, b). Thus, experimentalists may be exposed to the unexpected and potentially dangerous effects of LCMV owing to its non-cytolytic persistent infection in tissue culture cell lines and experimen- tal or pet animals. The recognized arenavirus diseases of man, the vectors and laboratory models used for their study are listed in Table 1. Study of the biology of LCMV has led to several major advances in contem- porary virology and immunology. For example, research on both the acute and persistent infection of mice with LCMV led to the first descriptions of virus induced immunopathologic disease (ROWE 1954), ofT cell mediated killing (COLE et al. 1973; MARKER and VOLKERT 1973) and of the two unique and separate signals necessary for recognition and lysis of virus infected targets by cytotoxic T lymphocytes (CTLs) (ZINKERNAGEL and DOHERTY 1974). Hence, study of the LCMV indicated that CTLs kill virus infected targets only when two conditions are met: recognition of virus specific determinants and matching of the major histocompatibility complex on the CTL and the infected target cell. This phenomenon ofMHC restriction, one of the major tenets of contempo- The Arenaviruses - An Introduction 3 rary immunology, was not only first described by experimentalists working with LCMV but also its implications were clearly recognized in this setting (reviewed by ZINKERNAGEL and DOHERTY 1979). Additionally, the components, kinetics, genetic control and deposition of immune complexes from the circula- tion into a variety of tissues including renal glomeruli, brain choroid plexus and blood vessel arteries were explored by utilizing the LCMV model (OLDSTONE and DIXON 1969). The conclusions were extended to work on numerous RNA and DNA virus infections as well as infections with other microbial agents (reviewed OLDSTONE 1975). Recently, by examination of its supposedly benign effect, LCMV was shown to cause disease not by means of the well-known anatomical viral induced destruction of infected cells, but rather by disordering the synthesis of such cells' differentiated products (OLDSTONE et al. 1982; re- viewed OLDSTONE 1984). These studies in animals indicate that viruses may cause disease by altering the cells' physiology and function without causing their destruction. If these findings are applicable to human viruses, in vivo, we can anticipate much-needed understanding of the mechanisms by which dysfunctions of endocrine, nervous and immune systems occur. Arenaviruses obtained their name from arenosus Latin for sandy - on the basis of characteristic fine granularities seen inside the virion on ultrathin section (ROWE et al. 1970). To avoid confusion between areno and adeno viruses, the International Committee on Viral Nomenclature changed the name to arena- viruses (ROWE et al. 1970). Recently, the ability of such viruses to cause persistent infection in cultured cells and animals, as well as their non-cytolytic nature, has been coupled with the wealth of information known about their biologic activity to inspire intensive investigation into the molecular control of viral genes and the molecular basis of arenavirus induced disease. It is the melding of newly obtained information on the viral chromosomes and gene structure, the proteins encoded by various viral genes and the ambisense (positive-genomic sense and negative-complemen- tary sense) organization of the arenavirus genome - particularly as relates to the molecular basis of viral persistence, tissue tropism, viral gene regulation and mechanism of pathogenesis and biology of the virus - that led to the selection of arenaviruses for these two volumes in the Current Topics in Microbi- ology and Immunology series. References Cole GA, Prendergast RA, Henney CS (1973) In vitro correlates of LCM virus-induced immune response. In: Lehmann-Grube F (ed) Lymphocytic Choriomeningitis Virus and Other Arenavir- uses. Springer, Berlin Heidelberg New York Grimwood BG (1985) Viral contamination of a subline of Toxoplasma gondii RH. Infect Immun 50:917-918 Grimwood BG, O'Connor G, Gaafar HA (1983) Toxofactor associated with Toxoplasma gondii infection is toxic and teratogenic to mice. Infect Immun 42: 1126-1135 Hinman AR, Fraser DW, Douglas RG Jr, Bowen GS, Kraus AL, Winkler WG, Rhodes WW (1975) Outbreak of lymphocytic choriomeningitis virus infections in medical center personnel. Am J Epidemiol101: 103-110 4 M.B.A. Oldstone Lehmann-Grube F (ed) (1973) Lymphocytic Choriomeningitis Virus and Other Arenaviruses. Sprin- ger, Berlin Heidelberg New York Marker 0, Volkert M (1973) In vitro measurement of the time course of cellular immunity to LCM virus in mice. In: Lehmann-Grube F (ed) Lymphocytic Choriomeningitis Virus and Other Arenaviruses. Springer, Berlin Heidelberg New York Oldstone MBA (1975) Virus neutralization and virus-induced immune complex disease: Virus-anti- body union resulting in immunoprotection or immunologic injury - two different sides of the same coin. In: Progress in Medical Virology. Karger, Basel Oldstone MBA (1984) Virus can alter cell function without causing cell pathology: Disordered func- tion leads to imbalance of homeostasis and disease. In: Notking AL, Oldstone MBA (eds) Con- cepts in Viral Pathogenesis. Springer, New York Oldstone MBA, Dixon FJ (1969) Pathogenesis of chronic disease associated with persistent lympho- cytic choriomeningitis viral infection. I. Relationship of antibody production to disease in neona- tally infected mice. J Exp Med 129:483-505 Oldstone MBA, Peters CJ (1978) Arenavirus infections of the nervous system. In: Handbook of Clinical Neurology. North-Holland, Amsterdam Oldstone MBA, Sinha YN, Blount P, Tishon A, Rodriguez M, von Wedel R, Lampert PW (1982) Virus-induced alterations in homeostasis: Alterations in differentiated functions of infected cells in vivo. Science 218: 1125-1127 Rowe WP (1954) Research Report NM 005 048.14.01. Nav Med Res Inst, Bethesda, Maryland Rowe WP, Murphy FA, Bergold GH, Casals J, Hotchin J, Johnson KM, Lehmann-Grube F, Mims CA, Traub E, Webb PA (1970) Notes Arenaviruses: Proposed name for a newly defined virus group. J Virol 5:651-652 Van der Zeijst BAM, Bleumink N, Crawford LV, Swyryd EA, Stark GR (1983a) Viral proteins and RNAs in BHK cells persistently infected by lymphocytic choriomeningitis virus. J Virol 48:262-270 Van der Zeijst BAM, Noyes BE, Mirault M-E, Parker B, Osterhaus ADME, Swyryd EA, Bleumink N, Horzinek MC, Stark GR (1983b) Persistent infection of some standard cell lines by lympho- cytic choriomeningitis virus: Transmission of infection by an intracellular agent. J Virol 48:249-261 World Health Organization (1975) International Symposium on Arenavirus Infections of Public Health Importance. Bull WHO 52:Nos. 4, 5, 6 Zinkernagel RM, Doherty PC (1974) Immunological surveillance against altered self-components by sensitized T lymphocytes in lymphocytic choriomeningitis. Nature (London) 251: 547-548 Zinkernagel RM, Doherty PC (1979) MHC-restricted cytotoxic T cells: Studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction specificity, func- tion, and responsiveness. Adv Immunol 27:51-177