Human T-Cell Leukemia Virus

265 Pages·1985·9.507 MB·English

by  Peter K. Vogt (auth.), Professor Dr. Peter K. Vogt (eds.)

Current Topics in
Microbiology
115 and Immunology
Editors
M Cooper, Birmingham/Alabama· H Eisen, Paris
W. Goebel, Wiirzburg . H Koprowski, Philadelphia
F. Melchers, Basel· M Oldstone, La Jolla/California
R Rott, GieBen . HG. Schweiger, Ladenburg/Heidelberg
P.K Vogt, Los Angeles· I. Wilson, La Jolla/California
Human T-Cell
Leukemia Virus
Edited by Peter K Vogt
With 74 Figures
Springer-Verlag
Berlin Heidelberg NewY ork Tokyo 1985
Professor Dr. PETER K. VOGT
University of Southern California
School of Medicine
Department of Microbiology
2025 Zonal Avenue HMR 401
Los Angeles, CA 90033, USA
ISBN-13:978-3-642-70115-3 e-1SBN-13: 978-3-642-70113-9
DOl: 10.1007/978-3-642-70113-9
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© by Springer-Verlag Berlin Heidelberg 1985
Softcover reprint of the hardcover 1st edition 1985
Library of Congress Catalog Card Number 15-12910
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2123/3130-543210
Table of Contents
P.K. VOGT: Human T-Cell Leukemia/Lymphoma
Viruses - An Introduction ......... 1
M. ROBERT-GUROFF, P.D. MARKHAM, M. POPOVIC,
and R.C. GALLO: Isolation, Characterization, and
Biological Effects of the First Human
Retroviruses: The Human T-Lymphotropic
Retrovirus Family. With 1 Figure 7
H. MITSUYA and S. BRODER: Human T-Cell
Leukemia/Lymphoma Viruses (HTLV): A Unique
Family of Pathogenic Retroviruses. With 2 Figures 33
K. T AJIMA and S. TOMINAGA: Epidemiology of Adult
T-Cell Leukemia/Lymphoma in Japan.
With 9 Figures .............. 53
W.A. BLATTNER and R.C. GALLO: Human T-Cell
Leukemia/Lymphoma Viruses: Clinical and
Epidemiologic Features . . . . . . . . . 67
K. TAKATSUKI, K. YAMAGUCm, F. KAWANO,
H. NISlllMURA, M. SEIKI, and M. YOSlllDA: Clinical
Aspects of Adult T-Cell Leukemia/Lymphoma 89
Y. ITO: The Epidemiology of Human T-Cell
Leukemia/Lymphoma Virus. With 5 Figures 99
M. SlllMOYAMA: Adult T-Cell Leukemia/Lymphoma
and Its Clinical Subtypes from the Viewpoints of
Viral Etiology . . . . . . . . . . . . . . . . 113
Y. HINUMA: A Retrovirus Associated with a Human
Leukemia, Adult T-Cell Leukemia . . . . . . . 127
I. MIYosm: Biology of Human T-Cell Leukemia Virus:
Search for an Animal System. With 7 Figures 143
VI Table of Contents
M. YOSHIDA, S. HATTORI, and M. SEIKI: Molecular
Biology of Human T-Cell Leukemia Virus
Associated with Adult T-Cell Leukemia.
With 9 Figures . 157
W.A. HASELTINE, J.G. SODROSKI, and R. PATARCA:
Structure and Function of the Genome of HTLV .
With 7 Figures ............... 177
F. WONG-STAAL: Some Perspectives on the
Molecular Mechanism of in Vitro Transformation
and in Vivo Leukemogenesis by HTLV .
With 3 Figures ............... 211
S. OROSZLAN and T.D. COPELAND: Primary Structure
and Processing of gag and env Gene Products of
Human T-Cell Leukemia Viruses HTLV-IcR and
HTLV-IATK• With 9 Figures .......... 221
R.A. WEISS, P. CLAPHAM, K. NAGY, and
H. HOSHINO: Envelope Properties of Human T-Cell
Leukemia Viruses. With 3 Figures ....... 235
T.J. PALKER, D.P. BOLOGNESI, and B.F. HAYNES:
Human T-Cell Leukemia/Lymphoma Virus:
Studies of Host-Virus Interaction. With 9 Figures .. 247
Indexed in Current Contents
List of Contributors
BLATINER, W.A., Environmental Epidemiology Branch,
National Cancer Institute, Landow Building, Bethesda,
MD 20205, USA
BOLOGNESI, D.P., Department of Surgery, Duke University
School of Medicine, P.O. Box 2926, Durham, NC 27710,
USA
BRODER, S., Clinical Oncology Program, National Cancer
Institute, Bethesda, MD 20205, USA
CLAPHAM, P., Institute of Cancer Research, Chester Beatty
Laboratories, Fulham Road, London SW3 6JB, Great
Britain
COPELAND, T.D., Laboratory of Molecular Virology and
Carcinogenesis, LBI-Basic Research Program, NCI
Frederick Cancer Research Facility, Frederick, MD
21701, USA
GALLO, R.C., Laboratory of Tumor Cell Biology, National
Cancer Institute, Bethesda, MD 20205, USA
HASELTINE, W.A., Laboratory of Biochemical Pharmaco
logy, Dana Farber Cancer Institute, Charles A. Dana
Cancer Center, 44 Binney Street, Boston, MA 02115,
USA
HATTORI, S., Department of Viral Oncology, Cancer Insti
tute, Kami-Ikebukuro, Toshimaku, Tokyo 170, Japan
HAYNES, B.F., Departments of Medicine and Surgery, Duke
University School of Medicine, Durham, NC 27710,
USA
HINUMA, Y., Institute for Virus Research, Kyoto Universi
ty, Shogoin-Kawaracho, Kyoto 606, Japan
HOSHINo, H., Virology Division, National Cancer Center
Research Institute, Tsukiji, Chuo-ku, Tokyo 104, Japan
ITO, Y., Department of Microbiology, Faculty of Medicine,
Kyoto University, Kyoto 606, Japan
KAWANO, F., The Second Department of Internal Medi
cine, Kumamoto University Medical School, Honjyo
1-1-1, Kumamoto 860, Japan
MARKHAM, P.D., Laboratory of Tumor Cell Biology, Na-
VIII List of Contributors
tional Cancer Institute, National Institutes of Health,
Bethesda, MD 20205, USA
MITSUYA, H., Clinical Oncology Program, National Cancer
Institute, Bethesda, MD 20205, USA
MIYOSHI, I., Department of Internal Medicine, Kochi Med
ical School, Nankoku City, Kochi 781-51, Japan
NAGY, K., Microbiological Research Group, National In
stitute of Hygiene, Piheno u-1, 1529, Budapest, Hungary
NISHIMURA, H., The Second Department of Internal Medi
cine, Kumamoto University Medical School, Honjyo
1-1-1, Kumamoto 860, Japan
OROSZLAN, S., Laboratory of Molecular Virology and Car
cinogenesis, LBI-Basic Research Program, NCI-Freder
ick Cancer Research Facility, Frederick, MD 21701,
USA
PALKER, T.J., Departments of Medicine and Surgery, Duke
University School of Medicine, P.O. Box 3258, Durham,
NC 27710, USA
PATARCA, R., Laboratory of Biochemical Pharmacology,
Dana Farber Cancer Institute, Charles A. Dana Cancer
Center, 44 Binney Street, Boston, MA 02115, USA
POPOVIC, M., Laboratory of Tumor Cell Biology, National
Cancer Institute, National Institutes of Health, Bethesda,
MD 20205, USA
ROBERT-GUROFF, M., Laboratory of Tumor Cell Biology,
National Cancer Institute, National Institutes of Health,
Bethesda, MD 20205, USA
SEIKI, M., Department of Viral Oncology, Cancer Institute,
Kami-Ikebukuro, Toshimaku, Tokyo 170, Japan
SHIMOYAMA, M., Departments of Clinical Laboratory and
Internal Medicine, National Cancer Center Hospital,
5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan
SODROSKI, J.G., Laboratory of Biochemical Pharmacology,
Dana Farber Cancer Institute, Charles A. Dana Cancer
Center, 44 Binney Street, Boston, MA 02115, USA
TAJIMA, K., Division of Epidemiology, Aichi Cancer Center
Research Institute, Kanokoden 81-1159, Tashiro-cho,
Chikusa-ku, Nagoya, Japan
TAKATSUKI, K., The Second Department ofInternal Medi
cine, Kumamoto University Medical School, Honjyo
1-1-1, Kumamoto 860, Japan
TOMINAGA, S., Division of Epidemiology, Aichi Cancer
Center Research Institute, Kanokoden 81-1159, Tashiro
cho, Chikusa-ku, Nagoya, Japan
WEISS, R.A., Institute of Cancer Research, Chester Beatty
Laboratories, Fulham Road, London SW3 6JB, Great
Britain
List of Contributors IX
WONG-STAAL, F., Laboratory of Tumor Cell Biology, Na
tional Cancer Institute, National Institutes of Health,
Bethesda, MD 20205, USA
Y AMAGUCm, K., The Second Department of Internal Medi
cine, Kumamoto University Medical School, Honjyo
1-1-1, Kumamoto 860, Japan
YOSIllDA, M., Department of Viral Oncology, Cancer Insti
tute, Kami-Ikebukuro, Toshimaku, Tokyo 170, Japan
Human T-Cell Leukemia/Lymphoma Viruses -
An Introduction
PETER K. VOGT
Retroviruses occur in all classes of vertebrates: in fishes, amphibians, reptiles,
birds, and mammals. Although some have cytocidal potential, most retroviruses
replicate without killing their cellular hosts. They are best known for their
ability to induce tumors: retroviruses are natural, infectious carcinogens. Retro
viruses can be transmitted vertically through the germ line as endogenous viral
agents that mayor may not be expressed during the lifetime of the animal.
Vertically transmitted and expressed retroviruses often become oncogenic, but
most retroviral tumors in outbred animal populations are caused by horizontal,
exogenous infections. Virus replication and transmission are part of the etiologi
cal chain for oncogenesis. Some retrovirus-induced tumors are overtly conta
gious under natural conditions, for example bovine and avian leukosis and
feline leukemia. In others infectious virus is absent, but epidemiological data
can provide evidence for the etiological role of a transmissible agent.
A search for a tumor-inducing virus can therefore follow two principal ap
proaches: it can look for evidence of complete or defective virus in fresh tumor
material and in tumor cell cultures, or it can examine epidemiological- data
for indications that a transmissible oncogenic agent is at work. In the discovery
of the first human retroviruses, the human T cell leukemia viruses (HTLV ),
both avenues played an important role. They were followed independently by
research groups working on different continents, but soon it became clear that
these independent paths converged and had led to the same disease and the
same virus.
The ubiquity of retroviruses and their frequent role as natural carcinogens
in animals inspired an intensive search for human retroviruses in the early
seventies, generously supported by the National Cancer Institute of the United
States through its Virus Cancer Program. This search was largely disappointing.
It turned up several candidate human retroviruses, but a more detailed charac
terization of these isolates proved them to be of probable animal origin. In
the ensuing disillusionment scientists increasingly turned to other tasks in onco
logy, and financial support for tumor virology declined. Throughout this time
only one group of virologists continued the seemingly unpromising search for
a retrovirus in human tumors. Their perseverance was rewarded in 1980 when
they isolated a new retrovirus from human T cell leukemia (POIESZ et al. 1980b).
This virus was different from the known retroviruses in structure and antigeni
city. It was found in fresh peripheral lymphocytes from a leukemic patient
as well as in cultured T cells derived from leukemic blood and therefore was
likely an authentic human virus. The new virus was termed human T cellieuke-
Current Topics in Microbiology and Immunology, Vol. 115
© Springer-Verlag Berlin· Heidelberg 1985
2 P.K. Vogt
mia virus, now more precisely referred to as HTLV - I. The discovery and isola
tion of HTLV-I came about through work on lymphocyte cell culture. Efforts
to establish long term T cell cultures succeeded, when a method for producing
T cell-derived growth factor, also known as interleukin 2, was found, and the
factor was added to the medium (MORGAN et al. 1976; POIESZ et al. 1980a).
Some of the T cell leukemia cultures established with the help of interleukin
2 became producers of HTLV-I, an activity first detected by the presence of
reverse transcriptase in the culture medium.
At about the same time epidemiological investigations on the types, inci
dence, and geographic distribution of lymphomas and leukemias in Japan led
to the recognition of adult T cell leukemia/lymphoma as a specific clinical
entity, and to the realization that this aggressive hemopoietic disorder occurred
much more frequently in the southwestern regions of Japan than in the rest
of the country (TAKATSUKI et al. 1977, 1979; TAJIMA 1979). Again, the establish
ment of continuous T cell leukemia-derived cell lines made it possible to follow
up this interesting observation (MIYOSm et al. 1979). Antibodies to a leukemia
cell surface antigen (adult T cell leukemia antigen, ATLA) were found in patients
with adult T cell leukemia and in their healthy family members. The distribution
of this immune reactivity in the population was consistent with the notion
that a transmissible agent was the cause of adult T cell leukemia/lymphoma
in southwestern Japan (HINUMA et al. 1981). Such a virus was soon detected
in the T cell cultures by electron microscopy (MIYosm et al. 1981). It was called
adult T cell leukemia virus (ATLV). ATLV and HTLV-I turned out to be
closely related immunologically, and recent work shows them to be virtually
identical, two different isolates of the same virus (WATANABE et al. 1984). Scien
tists working on this virus have agreed to use the term HTLV, because this
was the designation chosen in the first published description and characteriza
tion. However, early papers from Japan and even some current literature use
the abbreviation A TLV , which should be considered synonymous with HTLV -I.
Somewhat before the American and Japanese discoveries of HTLV, type C
retrovirus particles had been seen in T cell lymphomas, but this observation
was not followed up (VAN DER Loo et al. 1979).
The present volume contains a collection of papers by leading scientists
in the area of human T cell leukemia. The papers concentrate on the work
of the authors' own laboratories and place it in context with the HTLV field
as a whole. Thus, the book covers, from different vantage points, the epidemio
logy of HTLV, the connection of HTLV with human disease, and the cellular
and molecular biology of the virus. Following the historical development,
greater emphasis is placed on the leukemogenic potential of HTLV, but the
immunosuppressive capacity of the virus and the association of HTLV -III with
acquired immunodeficiency are considered as well. The book represents the
first 3 years in a new and exciting area of research, that of the first human
retroviruses. The picture emerging is that of a unique group of human pathogens
and of a unique class of retroviruses. The important observations, reported
and referenced in detail in the individual contributions of this book, can be
summarized as follows:
HTLV - infected cells contain one or more pro viruses integrated into chromo
somal DNA. The integrated provirus has been cloned and sequenced. It has