Epstein-Barr Virus and Human Cancer

233 Pages·2001·6.76 MB·English

by  B. Sugden, E. R. Leight (auth.), Professor Dr. Kenzo Takada (eds.)

Current Topics in
Microbiology
258 and Immunology
Editors
R.W. Compans, Atlanta/Georgia
M. Cooper, Birmingham/Alabama· Y. Ito, Kyoto
H. Koprowski, Philadelphia/Pennsylvania· F. Melchers, Basel
M. Old stone, La lolla/California . S. Olsnes, Oslo
M. Potter, Bethesda/Maryland
P.K. Vogt, La lolla/California . H. Wagner, Munich
Springer-Verlag Berlin Heidelberg GmbH
Epstein-Barr Virus
and Human Cancer
Edited by K. Takada
With 38 Figures and 13 Tables
, Springer
Professor Dr. KENZO TAKADA
Hokkaido University
Tnstitute for Genetic Mcdicine
Departmcnt of Tumor Virology
Nl5 W7. Kita-Ku
060-8638 Sapporo
Japan
e-mail: [email protected].
COI'er //lustration: BamHI fragment map for the EBV genome.
The outer open boxes are viral genes cxpressed during latent
infection in culture
ISSN 0070-217X
ISBN 978-3-642-62568-8 ISBN 978-3-642-56515-1 (eBook)
DOI 10.1 007/978-3-642-56515-1
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Preface
Epstein-Barr virus (EBV), a human herpesvirus, originally
received much attention because of its associations with Burkitt's
lymphoma and nasopharyngeal carcinoma. Subsequently it
turned out that EBV is ubiquitous in the human population and
most people carry the virus in memory B cells in a latent state.
Now, many other malignancies such as T/NK cell lymphoma,
AIDS-associated B-cell lymphoma, gastric carcinoma, and
Hodgkin's disease have been causally linked to EBV.
The development of molecular biology techniques has
allowed us to study the roles of individual EBV genes that act in
the maintenance and disruption of EBV latency. The outbreak of
AIDS revealed the oncogenic potential of EBV. AIDS-associated
B-cell lymphoma is a proliferation of EBV-infected B cells in the
absence of immune surveillance. This indicates that EBV-infected
B cells have the ability to produce tumors if the host immune
system does not work. The EBV-immortalized peripheral B cell is
an in vitro model of AIDS lymphoma, and has been the focus of
extensive studies. These studies revealed that latent membrane
protein I (LMPI) is particularly important for the immortaliza
tion of B cells. On the other hand, As for the role of EBV in
Burkitt's lymphoma and epithelioid malignancies including na
sopharyngeal carcinoma and gastric carcinoma, we initially could
not exclude the possibility that the virus was a passenger and had
no role in their carcinogenesis. However, the recent establishment
of in vitro models for Burkitt's lymphoma and epithelioid ma
lignancies proved that EBV could contribute malignant conver
sion of these tumor cells, thus excluding a passenger scenario.
In this volume, outstanding researchers from the United
States and Japan review recent progress in EBV research. I be
lieve that this book will help readers to understand what has been
done and what should be done in EBV research.
KENZO T AKADA
List of Contents
I Molecular Mechanisms of Maintenance
and Disruption of Virus Latency
B. SUGDEN and E.R. LEIGHT
EBV's Plasmid Replicon: An Enigma in cis and trans 3
K. HlRAlt and M. SHIRAKATA
Replication Licensing of the EBV oriP Minichromosome 13
S. FUJIWARA
Epstein-Barr Virus Nuclear Protein 2-Induced Activation
of the EBV-Replicative Cycle in Akata Cells:
Analysis by Tetracycline-Regulated Expression. . . 35
L.M. HUTT-FLETCHER and C.M. LAKE
Two Epstein-Barr Virus Glycoprotein Complexes. 51
T. TSURUMI
EBV Replication Enzymes ........ . 65
II EBV-Associated Malignancies
M. FUKAYAMA, J.-M. CHONG, and H. UOZAKI
Pathology and Molecular Pathology
of Epstein-Barr Virus-Associated Gastric Carcinoma. . . 91
K. AozAsA, H. KANNO, H. MlWA, and Y. TOMITA
EBV and Malignant Lymphoma with Special
Emphasis on Pyothorax-Associated Lymphoma 103
H. KATANa, T. SATA, and S. MaRl
AIDS Lymphoma: Its Virological Aspects 121
III Molecular Mechanisms of Oncogenesis
K. TAKADA
Role of Epstein-Barr Virus
in Burkitt's Lymphoma ................... . 141
VIII List of Contents
I.K. RUF, P.W. RHYNE, H. YANG, CM. BORZA,
L.M. HUTT-FLETCHER, J.L. CLEVELAND, and J.T. SAMPLE
EBV Regulates c-MYC, Apoptosis,
and Tumorigenicity in Burkitt's Lymphoma. . . . . . . . .. 153
S. IMAI, J. NISHIKAWA, M. KURODA, and K. TAKADA
Epstein-Barr Virus Infection
of Human Epithelial Cells. . . . . . . . . . . . . . . . . . . . . .. 161
T. SAIRENJI, M. TAJIMA, M. KANAMORI, N. TAKASAKA,
X. GAO, M. MURAKAMI, K. OKINAGA, Y. SATOH,
Y. HOSHIKAWA, H. ITo, Y. MIYAZAWA, and T. KURATA
Characterization of EBV-Infected Epithelial Cell Lines
from Gastric Cancer-Bearing Tissues. . . . . . . . . . . . . .. 185
IV Animal Model and New Therapeutic Approach
to Malignancy
F. WANG
A New Animal Model for Epstein-Barr
Virus Pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . .. 201
C.M. ROONEY, L.K. AGUILAR, M.H. HULS,
M.K. BRENNER, and H.E. HESLOP
Adoptive Immunotherapy of EBV -Associated
Malignancies with EBV -Specific Cytotoxic
T -Cell Lines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 221
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231
List of Contributors
(Their addresses can be found at the beginning of their respective
chapters.)
AGUILAR, L.K. 221 MIWA, H. 103
AozAsA, K. 103 MIYAZAWA, Y. 185
BORZA, CM. 153 MORI, S. 121
BRENNER, M.K. 221 MURAKAMI, M. 185
CHONG, J.-M. 91 NISHIKAWA, J. 161
CLEVELAND, J.L. 153 OKINAGA, K. 185
FUJIWARA, S. 35 RHYNE, P.W. 153
FUKAYAMA, M. 91 ROONEY, C.M. 221
GAO, X. 185 RUF, I.K. 153
HESLOP, H.E. 221 SAIRENJI, T. 185
HIRAI·I·, K. 13 SAMPLE, J.T. 153
HOSHIKAWA, Y. 185 SATA, T. 121
HULS, M.H. 221 SATOH, Y. 185
HUTT-FLETCHER, L.M. SHIRAKATA, M. 13
51, 153 SUGDEN, B. 3
IMAI, S. 161 TAJIMA, M. 185
ITo, H. 185 TAKADA, K. 141, 161
KANAMORI, M. 185 TOMITA, Y. 103
KANNO, H. 103 TSURUMI, T. 65
KATANO, H. 121 TAKASAKA, N. 185
KURATA, T. 185 UOZAKI, H. 91
KURODA, M. 161 WANG, F. 201
LAKE, CM. 51 YANG, H. 153
LEIGHT, E.R. 3
I
Molecular Mechanisms of Maintenance
and Disruption of Virus Latency
EBV's Plasmid Replicon: An Enigma in cis and trans
B. SUGDEN and E.R. LEIGHT
References . . 9
Epstein-Barr virus (EBV) is a strikingly successful human parasite infecting more
than 90% of humanity. It has adapted itself well to people; after primary infection,
it usually remains latent for life and infrequently causes disease. The diseases it does
cause, however, are often malignant. During latent infection, EBV maintains its
duplex DNA extrachromosomally as a circular molecule in both non proliferating
and proliferating cells. The lytic phase of EBV's life-cycle can only be initiated in
cells formerly supporting its latent phase. During the lytic phase, the plasmid
replicon is the initial template for amplification of viral DNA. EBV's plasmid
replicon is, therefore, an essential feature of both phases of EBV's life-cycle. The
elements of this viral plasmid have been studied both to understand their roles in
the life-cycle of this human pathogen and to gain any insights they might provide
into the synthesis and segregation of other viral and cellular replicons. Much has
been learned about this plasmid replicon, but much about it remains obscure.
Several defining features of the intact, viral, plasmid replicon have been es
tablished. The DNA of EBV was shown to be an extrachromosomal replicon in a
Burkitt's lymphoma-derived cell line and in nasopharyngeal carcinoma biopsies by
isolating large DNA from the cells and separating the DNAs as a function of their
densities in CsCI gradients (LINDAHL et al. 1975; KASHKA-DIERICH et al. 1976)
(Fig. la). EBV DNA contains 58% G + C while human DNA contains on the
average 42% G + C. The intact viral DNA banded at equilibrium at a density
appropriate for its being free of cellular sequences. The viral plasmid DNA was
shown to be synthesized once per cell cycle by labeling cells with bromodeoxyuri
dine (BrdU) and finding that EBV first became heavy/light in its density at the same
rate as did cellular DNA (ADAMS 1987). An origin of plasmid DNA synthesis
within the B95-8 strain of EBV was determined via two-dimensional gel electro
phoresis of replicative intermediates to map at or near its dyad symmetry (DS)
element (GAHN and SCHILDKRAUT 1989), an element required for efficient replica
tion of subgenomic, EBV-derived plasmids (YATES et al. 1984) (Fig. la). These
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA