Measles Virus and its Biology PDF
Preview Measles Virus and its Biology
EXPERIMENTAL VIROLOGY Series Editors: T. W. TINSLEY Director, Natural Environment Research Council Unit of Invertebrate Virology, Oxford, England and F. BROWN Head of Biochemistry Department, Animal Virus Research Institute, Pirbright, Surrey, England Measles Virus and Its Biology K. B. Fraser and S. J. Martin Measles virions from clarified infected vero cell extract. The particles are pleomorphic, heterogeneous in size and bear prominent spikes 12.5 nm in length. Preparation stained with 2 % phosphotungstic acid photographed on a Corinth 500 electron microscope. Magnification X 240,000. MEASLES VIRUS AND ITS BIOLOGY K. B. FRASER and S. J. MARTIN Department of Microbiology and Immunology and Department of Biochemistry The Queen's University of Belfast, Belfast, N. Ireland. 1978 ACADEMIC PRESS LONDON NEW YORK SAN FRANCISCO A Subsidiary of Harcourt Brace Jovanovich^ Publishers ACADEMIC PRESS INC. (LONDON) LTD. 24/28 Oval Road London NW1 United States Edition published by ACADEMIC PRESS INC. Ill Fifth Avenue New York, New York 10003 Copyright © 1978 by ACADEMIC PRESS INC. (LONDON) LTD. All Rights Reserved No part of this book may be reproduced in any form by photostat, microfilm, or any other means, without written permission from the publishers Library of Congress Catalog Card Number: 77-74369 ISBN: 0-12-265350-5 Printed in Great Britain by The Whitefriars Press Ltd., London and Tonbridge PREFACE This short monograph is not a compendium of all the published work on measles virus since it was last reviewed in extenso. It was written rather to acquaint the virologist with biological and clinical problems posed by this ubiquitous infection and equally to inform the clinical research worker about the behaviour of the virus which is one root of the phenomena that he sees in measles, whilst human biology is the other. In choosing facts and in referring to published work we have been influenced by two beliefs which we hold to be true. The first is that, viruses being sub-cellular entities, the ultimate explanation of any viro- logical process, be it in vitro or in vivo, will be biochemical or molecular- biological. The second is that, if there is any subject from which the study of virology can be divorced only by putting achievement in peril, that subject is immunology. Who would have supposed, only a few years ago, that the difference between acute and chronic infection of a suscep- tible cell might lie in an intrinsic defect of virus multiplication? Again, who would think that there can still be doubt as to whether immune processes cause chronic measles encephalitis, promote its establishment or simply fail to cure it? It seems to us therefore that measles virus is a most apposite example to fit within the framework of our two assertions. If the old facts and the new which we have gathered here do not so convince the reader, then the fault lies in poverty of authorship rather than lack of information. We are both greatly indebted to all members of the staffs of our depart- ments who do research on measles virus or who join with us in discussion and who have helped greatly with information from the work-bench and from the literature. Their individual contributions are acknowledged in illustrations, tables and references, as are those of overseas colleagues who have generously lent figures and data from their own publications. We have been greatly helped by Mr. W. D. Linton, Mr. A. Gilmore and the staff members of the Medical, Biomédical and Science libraries of the Queen's University of Belfast; by Miss C. Lyons, Mr. M. Killen, Mr. T. McLaughlin, and Mr. R. G. Wood who also helped greatly in preparing diagrams, micrographs and photographs. We are much indebted for our own electron micrographs to Dr. Evelyn Dermott. We acknowledge most gratefully the help of our typists, Miss E. G. Halliday, and particularly Mrs. A. Marshall who had the repetitious burden of arranging and com- pleting the main typescript. The Queens'' University of Belfast K. B. FRASER October, 1977 S. J. MARTIN I The biology of measles The Epidemiology of Measles . 3 The Pathogenesis of Measles 6 Stages of infection 6 Dissemination . . .. 7 Neurological complications of measles 8 Rare complications of measles 10 Comment . . . .. 11 INTERPRETATION— Two principal problems, if solved, could explain many of the complications of measles. These are: the mechanisms which produce persistent non-cytocidal infection by measles virus, and the relationships between measles virus and the immune system. Whether these factors are themselves inter- dependent in vivo is not yet known. There have been three developments which have aroused more interest in the nature of measles virus than has been shown since the virus was first isolated by Enders and Peebles in 1954 and then adapted to make a successful vaccine (Katz and Enders, 1959; Katz et al., 1962; Katz, 1965). The most powerful stimulus was the realization that measles virus antigen was implicated in subacute sclerosing panencephalitis (Sympo- sium, 1968), a rare but lethal disease of man, which was followed by the isolation of measles-like viruses from infected brain (Reviews: Connolly, 1972; ter Meulen et al., 1972b). The reasons why a very small proportion of children, previously infected with measles, should develop a fatal, chronic measles infection of the brain years later remain unknown and will be solved only by studying the biology of measles virus in relation to immunological and other factors in the patient (Chapter 9). The second development was unexpected. Killed measles vaccine, which was considered safer than live attenuated vaccine by many workers, not only failed to give complete protection against measles, 2 MEASLES VIRUS AND ITS BIOLOGY but also sensitized a certain number of those vaccinated in such a way that subsequent natural infection caused aberrant and sometimes serious symptoms. Of these symptoms, occasional severe pyrexia, the odd change in the distribution of the rash, the onset of respiratory symptoms and residual pulmonary lesions are not only of great intrinsic interest, but are quite sufficient to have stopped the use of killed measles virus with adjuvants as vaccine until some less provocative preparation can be prepared (Chapter 13). The third development is part of a new understanding that another chronic nervous disease, multiple sclerosis (which is much commoner than subacute sclerosing panencephalitis), has many features that suggest immunological disarrangement as a cause or consequence of the illness. Amongst these abnormalities, slightly altered and paradoxical specific reactions towards measles virus are characteristic. They consist of greater than average antibody titre towards measles virus along with slightly reduced cellular responses (Chapter 8). Nevertheless, though slight, they deserve to be investigated and that, in turn, requires more knowledge of measles virus than we have at present (Chapter 11). Another reason for being dissatisfied with our knowledge of measles virus may or may not be intrinsic to the virus, for it arises from a pro- blem which exists only in undernourished populations. This is a high mortality associated with lack of food, especially protein starvation (Table 1.1). In these circumstances the disease is as severe as it was 150 years ago in Western European countries which are now prosperous and relatively unaffected by mortality due to measles. It is insufficient TABLE 1.1 The mortality due to measles in tropical Africa Class of Case mortality Author Place patient percent. Morley Nigeria Hospital 22 (1962) admission McGregor The Village, 14.01-15.22 (1964) Gambia domestic Savage Zambia Hospital 30% (at peak, (1967) admission age 6-18 months). Morley et al. East In-patients 5.7% (1967) Africa THE BIOLOGY OF MEASLES 3 to say that this behaviour is solely a matter of undernourishment, for few virus infections have this particular effect. Working out the mech- anism behind this pathogenic process will be of the greatest interest and consequence for its cure and prevention. In writing this account of the biology of measles virus we have been indebted to several excellent reviews, particularly those of Enders et al (1957), Enders (1962), Enders-Ruckle (1963), Karzon (1962), Mc- Carthy (1959, 1962), Waterson (1965), Arakawa (1964) and Matumoto (1966). It has been impossible to avoid repeating much that has been written, but in so doing, we have tried to select properties and pheno- mena which are not yet completely described or understood in them- selves and also those which are most likely to have some bearing on the clinical and epidemiological features of measles virus to which we have alluded. THE EPIDEMIOLOGY OF MEASLES The natural history of measles virus is reflected in the epidemiology of the disease. Because there is no natural reservoir of infection but man, the changing incidence of measles in a community, which we call its epidemiology, is entirely governed by the immune status of the popula- tion, which in turn is conditioned by size, density, composition by age and by previous experience of the disease. The spread of infection and periodicity of epidemics has been successfully explained mathemati- cally (Soper, 1929; Greenwood, 1935; McKendrick, 1940; Black, 1966) in accordance with the size of a population and its previous immunologi- cal experience of measles (Figs. l.la,b). Thus measles tends to die out completely in communities of less than about 250,000 or so, according to birth rate, until re-introduced from without, when the great infecti- vity of the virus ensures its successful lodgement again. Nothing is known of what accounts for the excessive infectivity of measles virus but it almost certainly implies rapid multiplication at the mucous surface on which it first alights whether the victim is suscep- tible or immune. Symptoms and signs of invasion are indeed known to occur at this stage of infection. Serological studies suggest that mean titres of antibody to the virus do decline somewhat over the years (Black and Rosen, 1962), but more so in the absence of endemic or epide- mic measles (Brown et al., 1969), so that sub-clinical infections can be inferred to take place. On the other hand systemic invasion by the virus as judged by second attacks, which are rare, is not likely to recur. The inference for subacute sclerosing panencephalitis is that the condition is a long standing or re-activated quiescent infection of the nervous 4 MEASLES VIEUS AND ITS BIOLOGY 400 300 c/) • · z 2 200 a: uu h- Z 100 10 20 30 lOOy^/N FIG. 1.1. (a)Observed relation between epidemic period and population in cities (U.K.). (Figure from Bartlett, 1957, with permission), (b) Relation between duration of epidemic and population density in islands. (Figure from Black, 1966, with permission). THE BIOLOGY OF MEASLES 5 B 20 h ICELAND. (/) X z o 15 K o g NEW HEBRIDES · a. 10 h NEW CALEDONIA SOLOMON IS. W.SAMOA < FR. POLYNESIA D Û TONGA 5l· Λ/INPUT km2
The list of books you might like
