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A Practical Guide to Clinical Virology
Second Edition
A Practical Guide to Clinical Virology. Edited by L. R. Haaheim, J. R. Pattison and R. J. Whitley
Copyright
 2002 John Wiley & Sons, Ltd.
ISBNs: 0-470-84429-9 (HB); 0-471-95097-1 (PB)
A Practical Guide to Clinical Virology
Second Edition
Edited by
L. R. Haaheim
Professor of Medical Microbiology, Depar tment of Microbiology and
Immunology, University of Bergen, Bergen, Norway
J. R. Pattison
Director of Research, Analysis and Information, Department of Health,
London, UK
R. J. Whitley
Department of Pediatrics, The Children’s Hospital,
The University of Alabama at Birmingham,
Birmingham, USA
Copyright & 2002 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester,
West Sussex PO19 8SQ, England
Telephone (+44) 1243 779777
First edition published 1989
Reprinted February 1993, November 1994
This book is based on Ha
˚

ISBN 0 471 95097 1 pbk
Typeset by Dobbie Typesetting Ltd, Tavistock, Devon
Printed and bound in Great Britain by Biddles Ltd, Guildford, Surrey
This book is printed on acid-free p aper responsibly manufactured from sustainable forestry in which at
least two trees are planted for each one used for paper production.
CONTENTS
Contributors ix
Preface xi
Preface to 1st Edition xiii
Abbreviations xv
References for Further Reading xvii
1 Classification and Nomenclature of Human and Animal Viruses
Y. Ghendon 1
2 Viruses and Disease
G. Haukenes and J. R. Pattison 7
3 Laboratory Diagnosis of Virus Infections
G. Haukenes and R. J. Whitley 15
4 Antiviral Drugs
J. S. Oxford and R. J. Whitley 21
5 Virus Vaccines
L. R. Haaheim and J. R. Pattison 37
6 Enteroviruses: Polioviruses, Coxsackieviruses, Echoviruses
and Newer Enteroviruses
A L. Bruu 45
7 Polioviruses
A L. Bruu 47
8 Coxsackieviruses, Echoviruses and Enteroviruses 29–34 and 68–71
A L. Bruu 55
9 Rhinoviruses and Coronaviruses
I. Ørstavik 61

J. A. McCullers 167
24 Hepatitis A Virus
M. Degre
´
173
25 Hepatitis B Virus
G. L. Davis 179
26 Hepatitis C Virus
G. L. Davis 185
27 Hepatitis D Virus
G. L. Davis 191
vi
28 Hepatitis E Virus
M. Degre
´
195
29 Emerging Hepatitis Viruses
G. L. Davis 201
30 Parvovirus B19
J. R. Pattison 203
31 Retroviruses
A. B. Dalen 209
32 Human Immunodeficiency Virus (HIV)
B. A
˚
sjo
¨
213
33 Human T-Cell Lymphotropic Virus Type I and II
R. J. Whitley and G. Shaw 221

, Centre for Research in Virology, Department of
Microbiology and Immunology, The Gade Institute, University of Bergen,
PO Box 7800, N-5020 Bergen, Norway
Tel: +47 55 58 45 08; Fax: +47 55 58 45 12; E-mai l: birgitta.asjo@
vir.uib.no
Professor Bjarne Bjorvatn, Centre for International Health, University of
Bergen, Armauer Hansen’s Building, Haukeland Hospital, N-5021 Bergen,
Norway
E-mail:
Dr Anne-Lise Bruu, Mikrobiologisk laboratorium, Sykehuset: Vestfold HF,
Postboks 2168, Postterminalen, 3103, Tønsberg, Norway
Professor Are B. Dalen, Institute of Cancer Research, University of
Trondheim, Medisinsk Teknisk Centre, Norway
Tel: +47 22 04 22 86; Fax: +47 22 04 24 47; E-mail: gabriel.anestad@
folkehelsa.no
Gary L. Davis M.D., Director, Division of Hepatology, Medical Director, Liver
Transplantation, Baylor Unive rsity Medical Center, Dallas, Texas, USA
Professor Miklos Degre
´
, Institute of Medical Microbiology, Rikshospitalet
University Hospital, 0027 Oslo, Norway
Tel: +47 23 07 11 00; Fax: +47 23 07 11 10; E-mail:
Dr Yuri Ghendon, Research Institute for Viral Preparations, 1 Dubrovskaya
Street 15, 109088 Moscow, Russian Federation
Fax: 7 095 274 5710
Professor Lars R. Haaheim, Department of Microbiology and Immunology,
University of Bergen, Bergen High Technology Centre, POB 7800, N-5020
Bergen, Norway
E-mail:
Dr Neil A. Halsey, Johns Hopkins University, Department of International

Professor Terje Traavik, Institute of Medical Biology, Department of Virology,
N-9037 University of Tromsø, Norway
Professor Richard J. Whitley, The University of Alabama at Birmingham,
Department of Pediatrics, The Children’s Hospital Ambulatory Care Center
616, 1600 7th Avenue South, Birmingham, AL 35294-0011, USA
Tel: 001 205 934 5316; Fax: 001 205 934 8559; E-mail: r.whitley@peds.
uab.edu
Donna Wiger, MSc, The Norwegian Medicines Agency, Sven Oftedals vei 6,
N-0950 Oslo, Norway
E-mail:
Drs Randi and Arnt Winsnes , The Norwegian Medicines Agency, Sven Oftedals
vei 6, N-0950 Oslo, Norway
E-mail: ; ;

x
PREFACE
Since its first edition in 1989* the science of virology has moved forwards at an
impressive pace. Modern technology has unravelled many complex aspects of
the genetics, structure and immunology of viruses, wher eas the diagnosis and
treatment of our most common viral diseases have not enjoyed a similar
impressive development. However, recent years have given us several new
antivirals, and it is hoped that we will also see new and better vaccines for
general use, as well as better diagnostic tools.
In this pocket-sized handbook we have attempted to meet the need for
condensed and readily accessible information about viruses as agents of human
disease. We hope that this book will provide useful information for all health-
care professionals, in particular practising physicians, medical and nursing
students, interns and residents. We have included some new chapters on
hepatitis and herpes viruses to this new edition, whereas the arboviruses
chapter has been taken out.

main chapters are constructed in the same way with respect to headings and the
location of each subject within the chapter. The reader will for instance always
find ‘Epidemiology’ at the bottom of the fifth page of a main chapter. In order
to provide a brief overview a summary page containing an ab breviated form of
the subsequent information is located at the beginning of each chapter. The
cartoon drawings also break with convention. Perhaps they will not only
amuse you but prove to be instructive and leave a visual image of some salient
points.
The present book represents a development of a Norwegian book (Ha
˚
ndbok
i klinisk virologi, Universitetsforlaget, Bergen, 1983) edited by two of us (GH
and LRH). It is not a textbook but a guidebook, and we have therefore
included four comprehensive textbooks for further reading as references.
We hope this book will provide useful information for all health-care
professionals, in particular practising physicians, medical students, interns and
residents. If the book convinces readers that clinical virology is part of practical
everyday medicine, we will have succeeded in our aims.
Bergen and London
May 1989
GUNNAR HAUKENES
LARS R. HAAHEIM
Department of Microbiology and Immunology
University of Bergen
Bergen
JOHN R. PATTISON
Department of Medical Microbiology
University College and Middlesex School of Medicine
London
xiii

HBcAG
HBeAG
}
Hepatitis B virus core, e and surface antigens, respectively
HBsAG
HBIG Hepatitis B immunoglobulin
HBV Hepatitis B virus
HCV Hepatitis C virus
HDV Hepatitis D (delta) virus
HEV Hepatitis E virus
xv
HFRS Haemorrhagic fever with renal syndrome
HI(T) Haemagglutination inhibition (test)
HIV Human imm unodeficiency virus
HPS Hantavirus pulmonary syndrome
HPV Human papilloma virus
HSV Herpes simplex virus
HTLV Human T-cell leukaemia virus
IF(T) Immune fluorescence (test)
IgA
IgG
}
Immunoglobulins of the classes A, G and M, respectivel y
IgM
IL-2 Interleukin 2
JCV Strain of human polyoma virus
Lat. Latin
LCR Ligase chain reaction
N Neuraminidase
NANB Non-A, non-B (hepatitis)

A Practical Guide to Clinical Virology. Edited by L. R. Haaheim, J. R. Pattison and R. J. Whitley
Copyright
 2002 John Wiley & Sons, Ltd.
ISBNs: 0-470-84429-9 (HB); 0-471-95097-1 (PB)
1. CLASSIFICATION AND
NOMENCLATURE OF HUMAN AND
ANIMAL VIRUSES
Y. Ghendon
The present universal system for virus taxonomy includes family, genus and
species. Virus families and subfamilies are designated by terms ending
in -viridae and -virinae, respectively. Families represent clusters of genera of
viruses with apparently common evolutionary origin. Genera are designated by
terms ending in -virus. The criteria used for creating genera differ between
families.
Virus characteristics used for classification vary from simple to complex
structure, including nucleic acid and protei n composition, virion morphology,
strategy of replication, physical and chemical pro perties, etc.
More than 60 genera and about 25 famili es of human and animal viruses are
recognized. Table 1.1 contains data on some families and genera of viruses
infecting man.
1
Table 1.1 CLASSIFICATION OF HUMAN VIRUSES
Family
Subfamily
Genus Examples
Double-stranded DNA, enveloped virions
Poxviridae
Chordopoxvirinae Orthopoxvirus Smallpox (variola), vaccinia
Parapoxviruses Orf
Molluscipoxvirus Molluscum contagiosum viruses

Rubivirus Rubellavirus
Flaviviridae Flavivirus Yellow fever virus (arbovirus group
B)
Unnamed Hepatitis C virus
Coronaviridae Coronavirus Human coronavirus
(b) Negative-sense, non-segmented genome
Paramyxoviridae
Paramyxovirinae Paramyxovirus Parainfluenzaviruses 1 and 3
Morbillivirus Measles virus
Rubulavirus Mumps virus, parainfluenzaviruses 2
and 4
Pneumovirinae Pneumovirus Respiratory syncytial virus
Rhabdoviridae Lyssavirus Rabies virus
Vesiculovirus Vesicular stomatitis virus
Filoviridae Filovirus Marburg and Ebola viruses
(c) Negative-sense, segmented genome
Orthomyxoviridae Influenzavirus A, B Influenza A and B viruses
Influenzavirus C Influenza C virus
Bunyaviridae Bunyavirus Bunyamwera virus, La Crosse virus,
California encephalitis virus
Phlebovirus Sandfly fever virus, Sicilian virus,
Rift Valley fever virus, Uukuniemi
virus
Nairovirus Crimean–Congo haemorrhagic fever
virus
Hantavirus Hantaan virus, Seoul virus, Sin
Nombre virus, Puumala virus
continued
3
Table 1.1 continued

A Practical Guide to Clinical Virology. Edited by L. R. Haaheim, J. R. Pattison and R. J. Whitley
Copyright
 2002 John Wiley & Sons, Ltd.
ISBNs: 0-470-84429-9 (HB); 0-471-95097-1 (PB)
2. VIRUSES AND DISEASE
Virus ¼ originally ‘poisonous matter’.
G. Haukenes and J. R. Pattison
Viruses are the smallest known infectious agents. They are all built up of
nucleic acid and protein coat(s) and may in addition have an outer lipoprotein
envelope. They replicate in cells and may thereby lead directly to cell damage
and cause disease. Alternatively, the host defences may lead to cell damage as
they attempt to clear virus-infected cells.
TRANSMISSION/INCUBATION PERIOD/CLINICAL FEATURES
Virus infections are transmitted by inhalation, ingestion, inocula tion,
sexual contact or transplacentally. The incubation period differs greatly
and may range from a few days (e.g. the co mmon cold) to months (e.g.
hepatitis B).
SYMPTOMS AND SIGNS
Systemic: Malaise, Fatigue, Fever, Myalgia, Asthenia
Local: Rash, Diarrhoea, Coryza, Cough,
Lymphadenopathy, Neck Stiffness, Local Pain,
Pareses, Conjunctivitis
Most infections are acute and of short duration. Some viruses become
latent and may be reactivated, others are associated with persistent
replication and chronic disease.
COMPLICATIONS
The infection may involve organs other than the one most frequently
involved (e.g. orchitis in mumps). Complications may also result from
immunopathological reactions (e.g. postinfectious encephalitis in
measles) or from secondary bacterial infections (e.g. bacterial