Table Of ContentThe Bloomsbury Series in Clinical Science
Titles in the series already published:
Bronchoalveolar Mast Cells and Asthma
K. C. Flint
Platelet-Vessel Wall Interactions
Edited by R. Michael Pittilo and Samuel J. Machin
Oxalate Metabolism in Relation to Urinary Stone
Edited by G. Alan Rose
Diseases in the Homosexual Male
Edited by Michael W. Adler
Forthcoming titles in the series:
Lasers in Urology: Theory and Practice
Edited by T. A. McNicholas
Parasitic Infections in Clinical Practice
G. C. Cook
The Parotid Gland
M. Hobsley and G. T. Watkin
The Blood Brain Barrier for Clinicians
Alan Crockard and Nicholas Todd
Disorders of Lipoprotein Metabolism
D. J. Betteridge
Immunology of Mycobacterial Infection
G.A. W.Rook
·H ERPES SIMPLEX
VIRUS
Adrian Mindel
With 51 Figures
Springer-Verlag
London Berlin Heidelberg New York
Paris Tokyo
Adrian Mindel, MB, BCh, MSc, MRCP
Senior Lecturer and Honorary Consultant in Genito-Urinary
Medicine, Academic Department of Genito-Urinary Medicine,
University College and Middlesex School of Medicine, James
Pringle House, The Middlesex Hospital, London WIN 8AA, UK
Series Editor
Jack Tinker, BSc, FRCS, FRCP, DIC
Director, Intensive Therapy Unit, The Middlesex Hospital,
London WIN 8AA, UK
Cover illustrations: background - Fig. 7 .lc; foreground upper
Fig. 7.4; foreground lower - Fig. 4.13.
British Library Cataloguing-in-Publication Data
Mindel, Adrian, 1949-
Herpes simplex virus.
1. Man. Herpes simplex
I. Title II. Series
616.5'2
Library of Congress Cataloging-in-Publication Data
Mindel, Adrian, 1949-
Herpes simplex virus/Adrian Mindel.
p. cm. - (The Bloomsbury series in clinical science)
Bibliography: p.
Includes index.
ISBN-13: 978-1-4471-1685-1 e-ISBN-13: 978-1-4471-1683-7
DOl: 10.1007/978-1-4471-1683-7
1. Herpes simplex. 2. Herpes simplex virus. I. Title.
II. Series.
RC147.H6M561989
616. 9 '25---dc19
89-30659
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, reprinting, re-use
of illustrations, recitation, broadcasting, reproduction on microfilms or in other
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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 1989
Softcover reprint of the hardcover 1s t edition 1989
The use of 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 pharmaceutical
literature.
Typeset by Goodfellow & Egan Limited, Cambridge
2128/3916-543210-Printed on acid-free paper
Series Editor's Foreword
Herpes Simplex Virus is the fifth monograph to be published in the
Bloomsbury Series of Clinical Science. It provides an authoritative
review of the key issues related to this common clinical problem.
The characteristics of the virus, its epidemiology and the diag
nosis and management of the various forms of infection are all
considered.
Adrian Mindel is an international authority on this subject; he
joined the Academic Department of Genito-urinary Medicine at
the Middlesex Hospital in 1980 and has been actively involved in
HSV research since that time. His major research interests include
the epidemiology and treatment of genital herpes, the epidemi
ology of neo-natal herpes and the many and varied features of
HSV infections in immuno-compromised patients.
The continuing aim of the Bloomsbury Series is to identify the
growing areas of clinical research and relate these to current and
future medical practice. In Herpes Simplex Virus such aspirations
have been successfully achieved.
London, May 1989 Jack Tinker
Preface
There has been considerable interest in herpes simplex viruses
(HSV) over recent years. Amongst the many reasons for this are
the introduction of safe and efficacious therapy, the recognition
that HSV may cause life-threatening infections in neonates and
immunocompromised patients, the observation that genital herpes
is one of the commonest viral sexually transmitted diseases and the
possible association of HSV with cervical cancer.
Whilst it is now well established that HSV is often subclinical
and that the virus establishes latency, our understanding of the
natural history, pathogenesis and pathology of HSV infections is
still somewhat patchy. The introduction of type-specific serological
assays and the numerous advancements in molecular biology are
now helping to unravel these complex issues.
This monograph is an attempt to bring together the clinical,
epidemiological, immunological, pathological and virological
aspects of HSV infections. It is written from a clinical perspective
and therefore clinical features, diagnosis and treatment constitute
the majority of the book. The sections on Virology, Immunology,
Epidemiology, Pathology and Pathogenesis are relatively brief but
I believe essential for a complete understanding of HSV infection.
November 1988 A.M.
Acknowledgements
I would like to thank Dr David Katz and Professor John Pattison
for their help and advice, Stuart Nightingale and Angela Scott for
their assistance with the preparation of the figures, Michael
Jackson without whose persistence and persuasion this project
would never have come to fruition, Katerina Ayres for typing the
manuscript, my two Research Nurses, OrIa Carney and Anna
Faherty, for their help in the conduct of clinical studies, and finally
all the patients who have participated in clinical studies at the
Middlesex Hospital over the last eight years, without whose help
none of this would have been possible.
Contents
1 Virology and Immunology .......................................... 1
2 Latency and Oncogenesis ............................................ 15
3 Epidemiology .......................................................... 33
4 Clinical Features: Locally Defined Sites .......................... 47
5 Clinical Features: Disseminated Infection ....................... 75
6 Pathology and Pathogenesis ........................................ 97
7 Laboratory Diagnosis ................................................ 115
8 Treatment, Prevention and Control .............................. 129
SUbject Index ............................................................. 161
Chapter 1
Virology and Immunology
Introduction
There are two herpes simplex viruses (HSV) designated HSV 1 and HSV 2.
Although the two viruses are morphologically identical and have approximately
50% DNA similarity, there are a number of biological, biochemical, genomic
and clinical differences between them. These are summarised in Table 1.1. The
clinical differences will be highlighted in subsequent chapters, but here I will
cover the basic virology and immunology of HSV infection.
Table 1.1. Comparison between HSV 1 and HSV 2
HSVI HSV2
Biological differences
Replication in chick Poor Form plaques
embryos
Sensitivity to BVDU Sensitive Insensitive
Neurovirulence in mice + +++
Livers of infected mice Microscopic lesions Macroscopic lesions
EM of infected cells Microtubular structures
Biochemical differences
DNA guanine + cytosine
content (mole %) 67 69
Genomic differences - 50% DNA sequence
similarity
Clinical differences
Oral infection +++ +
Genital infection + +++
Eye infection ++ +
Brain infection ++ +
Neonatal infection + ++
Disseminated infection + +
EM, electron microsopy; + etc., degree of reaction; BVDU, bromovinyl deoxyuridine.
2 Herpes Simplex Virus
D
Fig. 1.1. Structure of herpes simplex virus.
A Viral glycoproteins: gB is required for infectivity, gC combines with C3b complement component,
gD induces neutralising antibodies, gE binds to the FC portion of IgG, and gG is type specific for
HSV 1 and for HSV 2. B Envelope. C Tegument containing specific proteins. D Capsid. EDNA.
Virology
Structure of HSV
The herpes virion consists of a DNA core, an iscosohedral capsid containing
capsomers and an envelope. Between the capsid and the envelope is a structure,
called the tegument, consisting of fibrous proteins. The diameter of the total
enveloped virion measures 250 nm and that of the nucleocapsid approximately
100 nm (Fig. 1.1).
Envelope
The envelope is the outer covering of the virus, which is derived from modified
host cell membranes as the DNA-containing capsid breaks through the nuclear
membrane of the host cell (Roizman and Furlong 1974). It consists of a lipid
bi-layer with five types of glycoprotein embedded in it. These glycoproteins
mediate attachment of the virus to the host cell and are also important in
