Retrovirus Infections of the Nervous System: Current and Future Perspectives

179 Pages·1990·4.985 MB·English

by  M. B. Gardner (auth.), Michael B. A. Oldstone M.D., Hilary Koprowski M.D. (eds.)

Current Topics in
Microbiology
160 and Immunology
Editors
R. W. Com pans, Birmingham/Alabama . M. Cooper,
Birmingham/Alabama . H. Koprowski, Philadelphia
I. McConnell, Edinburgh . F. Melchers, Basel
V. Nussenzweig, New York· M.Oldstone,
La Jolla/California· S. Olsnes, Oslo . M. Potter,
Bethesda/Maryland· H. Saedler, Cologne· P. K. Vogt, Los
Angeles· H. Wagner, Munich I. Wilson, La Jolla/California
Retrovirus Infections
of the Nervous System
Current and Future Perspectives
Edited by
M. B. A. Oldstone and H. Koprowski
With 16 Figures
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo HongKong
MICHAEL B. A. OLDSTONE, M.D.
Dept. of Neuropharmacology, Scripps Clinic and Research Foundation,
10666 N. Torrey Pines Road, La Jolla, CA 92037, USA
HILARY KOPROWSKI, M.D., Direktor
The Wistar Institute, 36th Street at Spruce, Philadelphia.
PA 19104, USA
ISBN-13:978-3-642-75269-8 e-ISBN-13:978-3-642-75267-4
001: 10.1007/978-3-642-75267-4
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Preface
Although retroviruses have long been associated with a variety
of animal diseases, active research in the field of human
retroviruses dates from the discovery of human immunodefici
ency virus (HIV) in association with acquired immunodefici
ency syndrome (AIDS). The enormous research efforts in this
field have been directed toward understanding the nature of the
virus and toward its elimination through preventive vaccin
ation and the cure of the disease.
Human T-cell leukemia virus (HTLV-l) was the first
member of the human retrovirus family to be discovered. It
was implicated as the cause of adult T-cell leukemia (ATL)
even before the association of HIV and AIDS was established.
Research on HTLV - 1 has, however, been lagging behind that
of HIV because of the importance of AIDS. Today HTLV-1
and possibly closely related HTLV-2 are associated with a
variety of human neurologic diseases, and research activities
in this field may show that human retroviruses can cause a
variety of human diseases in addition to those affecting the
nervous system.
Papers in this volume attempt to acquaint the reader with
the present state of research into retrovirus infection and related
diseases of the nervous system.
Prominent among diseases of experimental and domestic
animals caused by retroviruses are demyelinative disorders,
arthritic and rheumatic illnesses, and progressive motor neuron
disorders. The wild mouse ecotropic virus causes a disease
that is discussed in the chapters by GARDNER and
PORTIS. GARDNER first described the disease in wild ("outbred")
mouse populations and he has contributed to defining the
susceptibility/resistance genes that control this infection.
PORTIS has been studying the disorder in inbred populations
and mapping the viral gene(s) involved. The study of wild mouse
ecotropic virus demonstrates how a retrovirus functions in a
genetically defined and manipulable experimental animal to
cause slow, progressive disease and points up the similarities
VI Preface
between this disorder and the human disease, am yo tropic
lateral sclerosis.
To define viral genes and products in murine retrovirus
neurologic disease, WONG has developed temperature
sensitive mutants, variants, and revertants of Moloney murine
leukemia virus and studied their ability to cause neurologic
disease. Although MCGUIRE deals not with retroviruses but
with lentiviruses infection, the caprine disease of the CNS
provides a good model for the study of human retrovirus
infection. The chapter by LACKNER et al. reports the study of
retrovirus infection in nonhuman primates and describes the
pathogenesis of the disease in the species nearest to the human
host.
In the section on human retrovirus infections, McFARLIN
and KOPROWSKI deal with the presence ofHTLV-l or HTLV-l
related virus in tissues of patients with chronic progressive
myelopathies such as tropical spastic paraparesis/HTLV - 1-
associated myelopathy syndrome and multiple sclerosis. At
tempts to produce an HTLV-l transgenic mouse model are
described by NERENBERG. The three other chapters in this
section deal with infections of the nervous system by HIV.
GNANN and OLDSTONE describe the precise diagnostic tools
necessary to distinguish among infections caused by the variety
of HIV strains. Attempts to identify a "neurotropic" strain of
HIV are described by CHENG-MEYER and LEVY. Finally, the
pathogenesis of nervous system infection by HIV is dealt with
by WILEY and NELSON.
The editors realize that this volume covers only a fraction of
research activity in the field of human retroviruses and neuro
logic diseases. They hope, however, that this publication will
promote better understanding of the role of these viruses in a
variety of human and animal disease and that this will increase
the interest in research in this important area.
Michael B. A. Old stone
La Jolla, CA
Hilary Koprowski
Philadelphia, PA
List of Contents
I. Animal Retrovirus Infections of the Nervous System
M. B. GARDNER: Genetic Resistance to a Retroviral
Neurologic Disease in Wild Mice . . . . . . 3
1. L. PORTIS: Wild Mouse Retrovirus: Pathogenesis 11
P. K. Y. WONG: Moloney Murine Leukemia Virus
Temperature-Sensitive Mutants: A Model for
Retrovirus-Induced Neurologic Disorders 29
T. C. MCGUIRE, K. I. O'ROURKE, D. P. KNOWLES,
and W. P. CHEEVERS: Caprine Arthritis Encephalitis
Lentivirus Transmission and Disease . . . .. 61
A. A. LACKNER, L. 1. LOWENSTINE, and P. A. MARX:
Retroviral Infections of the CNS of Nonhuman
Primates . . . . . . . . . . . . . . .. 77
II. Human Retrovirus Infections of the Nervous System
Human T-Cell Leukemia Virus Type 1 Infections of
the Nervous System
D. E. McFARLIN and H. KOPROWSKI: Neurological
Disorders Associated with HTLV -1 . . . . .. 99
M. I. NERENBERG: An HTLV-l Transgenic Mouse
Model: Role of the Tax Gene in Pathogenesis in
Multiple Organ Systems. . . . . . . . . 121
Human Immunodeficiency Virus Infections of the
Nervous System
1. W. GNANN, lr. and M. B. A. OLDSTONE: Using
Synthetic Peptide Reagents to Distinguish Infections
Caused by Different HIV Strains. . . . . . 131
C. CHENG-MAYER and 1. A. LEVY: Human
Immunodeficiency Virus Infection of the CNS:
Characterization of "Neurotropic" Strains . . 145
VIII Contents
c. A. WILEY and J. A. NELSON: Human
Immunodeficiency Virus: Infection of the Nervous
System. 157
Subject Index 173
List of Contributors
(Their addresses can be found at the beginning of their
respective chapters)
CHEEVERS, W. P. MARX, P. A.
CHENG-MAYER, C. McFARLIN, D. E.
GARDNER, M. P. MCGUIRE, T. C.
GNANN, 1. W. NELSON, J. A.
KNOWLES, D. P. NERENBERG, M. 1.
KOPROWSKI, H. OLDSTONE, M. B. A.
LACKNER, A. A. O'ROURKE, K. I.
LEVY, J. A. PORTIS, J. L.
LOWENSTINE, L. G. WILEY, C. A.
I. Animal Retrovirus Infections
of the Nervous System
Genetic Resistance to a Retroviral Neurologic
Disease in Wild Mice
M. B. GARDNER
I Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3 Discovery and Characterization of Akvr-I/FV-4 . . . . . . . . . . . . . . . . . . . . . . . . 6
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1 Introduction
The only known example of a naturally occurring oncoviral neurologic disease in
animals is the fatal hind leg paralysis described in an aging population of wild
mice (Mus musculus) from an isolated squab farm near Lake Casitas (LC) in
southern California (OFFICER et al. 1973; GARDNER et al. 1973). The disease,
called spongiform polioencephalomyelopathy, is caused by an infectious
(ecotropic) murine leukemia virus (MuLV) and is characterized by a nonin
flammatory, nonimmunogenic, direct retrovirus injury to anterior horn neurons
in the lumbosacral spinal cord. The observation that this virus and its associated
paralysis are detected in only a small minority (10%) of the LC mice is explained
by the segregation in this outbred population of a dominant ecotropic-MuLV
restriction gene, initially called Akrv-J and now called FV-4. In this chapter I
briefly summarize the natural history of this retroviral neurologic disease, for
which several recent reviews are available (GARDNER 1978; GARDNER and
RASHEED 1982; GARDNER 1985), and cover more recent information on the
discovery, structure, and function of this M uLV restriction gene.
2 Natural History
The major natural history features of the M uLV neurologic disease in LC wild
mice are listed in Table 1. There are two classes of infectious M uLV present in LC
mice; one class is called amphotropic because of a broad in vitro host range for
Department of Medical Pathology, University of California, Davis, California 95616, USA
Current Topics in Microbiology and Immunology, Vol. 160
© Springer-Verlag Berlin' Heidelberg 1990