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Journal of Virology, January 2001, p. 533-539, Vol. 75, No. 1
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.1.533-539.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Induction of Host Gene Expression following
Infection of Chicken Embryo Fibroblasts with Oncogenic Marek's
Disease Virus
Robin W.
Morgan,*
Luc
Sofer,
Amy S.
Anderson,
Erin L.
Bernberg,
Jing
Cui, and
Joan
Burnside
Delaware Agricultural Experiment Station,
Department of Animal and Food Sciences, College of Agriculture and
Natural Resources, University of Delaware, Newark, Delaware 19717-1303
Received 29 June 2000/Accepted 28 September 2000
 |
ABSTRACT |
Microarrays containing 1,126 nonredundant cDNAs selected from a
chicken activated T-cell expressed sequence tag database
(http://chickest.udel.edu) were used to examine changes in host cell
gene expression that accompany infection of chicken embryo fibroblasts
(CEF) with Marek's disease virus (MDV). Host genes that were
reproducibly induced by infection of CEF with the oncogenic RB1B strain
of MDV included macrophage inflammatory protein, interferon response
factor 1, interferon-inducible protein, quiescence-specific protein,
thymic shared antigen 1, major histocompatibility complex (MHC) class I, MHC class II, 
2-microglobulin, clusterin,
interleukin-13 receptor alpha chain, ovotransferrin, a serine/threonine
kinase, and avian leukosis virus subgroup J glycoprotein.
| |
TEXT |
Marek's disease (MD) is a
lymphoproliferative disorder of chickens caused by a herpesvirus,
Marek's disease virus (MDV) (5). MDV initially infects
chickens via the respiratory tract and then causes early cytolytic
infection in B cells followed by latent infection in T cells. In some
infections, MDV transforms CD4+ T cells and results in the
formation of massive lymphomas in a variety of tissues. MD has been
controlled in the commercial poultry industry since 1970 by the use of
live, nononcogenic vaccines; however, the mechanism of vaccine-induced
immunity is not well understood. Vaccination efficiently prevents tumor
formation but does not stop infection. As a result, variants of MDV
with enhanced virulence have emerged throughout the second half of this
century, and periodically new vaccines or vaccine regimens must be
introduced to adequately control field challenges. Little is known
about virus-host cell interactions that relate to MDV pathogenicity.
Microarrays have been widely applied to analyze gene expression changes
on a genome wide scale. They have been used to assess differences in
yeast transcription among strains in general (39), during
growth under various conditions such as heat or cold shock (27), during growth using different carbon sources
(27), and during aerobic versus anaerobic growth
(11). High-density arrays have been used to identify yeast
genes whose expression depends on transcriptional initiation factors
(21), to profile gene expression changes that accompany
activation of mouse T cells (41), and to explore and
compare signal transduction pathways (14, 28). They have
been used to identify human genes involved in the pathology of diseases
such as rheumatoid arthritis and inflammatory bowel disease
(17), to compare gene expression in cells expressing
either a transformed or a nontransformed phenotype (12,
46), and to study hematopoietic differentiation
(40). In combination with cluster analysis, microarrays
have been used to assess variation in gene expression patterns of human
cancers as a means to classify solid tumors (34). In plant
genomics, microarrays have been exploited to examine differential gene
expression for Arabidopsis (38). Microarray
analysis is widely recognized as a key tool in drug discovery
(16). With regard to virus infections, microarrays have
been used to assess changes in host cell gene expression following
human cytomegalovirus (HCMV) infection (49) and to
characterize temporal classes of HCMV gene expression (7).
Microarrays.
Our microarray was designed to contain as many
genes as possible with minimal redundancy. Sequences included were
chosen from our poultry activated T-cell database (43).
Cytokines, cytokine receptors, chemokines, and factors involved in
apoptosis, transcription, and T-cell activation were among the arrayed
cellular cDNAs. Inserts from selected clones were amplified using PCR
and vector-specific primers. PCR products were examined by agarose gel
electrophoresis for quality, yield, and concentration. Following
alcohol precipitation, PCR products were resuspended in 2× SSC (1×
SSC is 0.15 M NaCl plus 0.015 M sodium citrate) and stored in 96-well
format. Using a Flexys robot (Genomic Solutions, Ann Arbor, Mich.),
samples were spotted (5 ng in 40 nl) onto 5- by 7-cm nylon membranes at a density of 2,418 spots per membrane. In addition to 26 positive and
negative controls, each microarray contained 1,126 chicken activated
T-cell cDNAs, 32 MDV sequences, and 51 herpesvirus of turkeys
sequences, each spotted in duplicate. Once printed, membranes were
treated using standard procedures for adhering DNA to nylon. Presence
of DNA was confirmed by hybridization to a radiolabeled probe for the
multiple cloning region of the vector. The sensitivity and linear range
of array analysis was determined by hybridizing filters to increasing
amounts of labeled RNA. The linear range covered at least 2 orders of
magnitude, with inputs of 5 × 106 to 5 × 108 cpm [0.05 to 5 µg of poly(A) RNA].
Cultures of secondary chicken embryo fibroblasts (CEF; 1.2 × 107 cells per 75-cm2 tissue culture flask) were
mock infected or infected with cell-associated RB1B (105
PFU per flask) at passage level 18 and incubated for either 48 h
or 96 h. Total RNA was purified using guanidinium isothiocyanate followed by centrifugation through cesium chloride.
Poly(A)+ RNA was purified using a PolyATtract mRNA
isolation system (Promega, Madison, Wis.). Poly(A)+ mRNA
(0.5 to 1 µg) was heat denatured and annealed to oligo(dT) (1 µg).
Thereafter, the RNA was incubated with 3 mM dithiothreitol, 0.8 mM
dATP, dGTP, or dTTP, 40 U of RNasin, 100 µCi of
[
-32P]dCTP, and 400 U of Superscript II reverse
transcriptase (Life Technologies, Gaithersburg, Md.) in a total volume
of 30 µl of the manufacturer's recommended buffer at 42°C for
1 h. Labeled cDNA was purified using a ProbeQuant G-50 Micro
Column (Amersham Pharmacia Biotech Inc., Piscataway, N.J.). cDNAs were
labeled to a specific activity of about 108 cpm/µg of
poly(A)+ RNA.
Hybridization of cDNAs to membrane arrays was similar to protocols
routinely used for DNA hybridizations except that filters
were
prehybridized for 1 h at 48°C in 6 ml of hybridization solution
containing sheared, denatured chicken genomic DNA (50 µg/ml) and
salmon sperm DNA (100 µg/ml). For additional blocking, 50 µg of
chicken genomic DNA was added to the entire probe reaction prior
to
denaturation for 2 min at 98°C. Hybridization took place overnight
at
48°C. Following hybridization, filters were washed to high
stringency
and exposed to phosphorimager screens, which were scanned
using a Storm
PhosphorImager (Molecular Dynamics, Sunnyvale, Calif.)
TIFF files were
imported to a Sun workstation (Sun Microsystems,
Inc., Palo Alto,
Calif.) for analysis using Visage high-density
grid analysis software
(Genomic Solutions). Spreadsheets were
merged with Excel files
containing addresses and identities of
each spot. Excel spreadsheets
used in this study are accessible
at the University of Delaware chicken
expressed sequence tag website
(
http://chickest.udel.edu).
Induced host gene expression.
Differences in host gene
expression following infection of CEF with MDV were easily detected.
Signals on arrays hybridized with cDNA from MDV-infected CEF were
considered further if they were present in duplicate and differed
2-fold or more from signals on arrays hybridized with cDNA from
uninfected CEF. Normalization among arrays was done using global
normalization (http: //www.geneindex.org), a procedure in
which the output from each array is multiplied by a normalization
factor such that the average signal intensities of all arrays are equivalent.
All host genes showing twofold or greater induction above the
uninfected cell background at either 2 or 4 days postinfection
(dpi) in
either of two replicate experiments are shown (Fig.
1).
Twenty-one host genes in one
experiment and 22 in the other appeared
induced at either 2 or 4 dpi,
the overlap between the two replicate
experiments being 13 genes (Fig.
2). We have elected to maintain
the
cutoff for further consideration in both experiments at twofold,
a
value of minimum stringency that may allow identification of
some false
positives. All of these data can be accessed, downloaded,
and
subsequently manipulated from our website
(
http://chickest.udel.edu)
for individuals wishing to analyze
them more stringently or using
customized software tools. Table
1 indicates the relative induction
of
each species at both 2 and 4 dpi. In some cases, the patterns
of
expression were similar in the two experiments; i.e., genes
that were
expressed more heavily at 2 dpi than at 4 dpi showed
the same trend in
both trials. In other cases, trends for the
two experiments were not
the same. The species that were induced
most strongly (fivefold or
greater in both replicates at either
time point) in these experiments
were macrophage inflammatory
protein (MIP), quiescence-specific
protein, and interferon (IFN)
response factor 1 (IRF-1). Species that
were moderately (fivefold
or greater in one experiment and twofold or
greater in the other)
or somewhat (threefold or greater in one
experiment and twofold
or greater in the other) induced included
2-microglobulin, major
histocompatibility complex (MHC)
class II, thymic shared antigen
1 (TSA-1; also known as stem cell
antigen 2), IFN-inducible protein,
avian leukosis virus (ALV)
subgroup J (ALV-J) envelope glycoprotein,
and clusterin. Weakly
(approximately twofold in both experiments)
induced species included
interleukin-13 (IL-13) receptor alpha
chain (IL-13R
), MHC class I, a
serine/threonine kinase, and ovotransferrin.
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FIG. 1.
Induction of host gene expression following infection of
CEF with MDV. For experiment 1 (A) and 2 (B), data are presented as
fold induction above the background microarray, which was hybridized
with cDNA from uninfected CEF. All samples that were twofold or greater
above the background in duplicate spots on either the 2-dpi microarray,
the 4-dpi microarray, or both microarrays are shown. Each bar
represents the average of duplicate spots on the microarrays. LCK,
p56lck; TRAM, translocating chain-associating
membrane; ETK, epithelial and endothelial tyrosine kinase; BP, binding
protein; HSP, heat shock protein; cMIF, macrophage migration inhibitory
factor.
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FIG. 2.
Venn diagram showing relationship between induced genes
in experiments 1 and 2. Numbers in parentheses indicate maximum fold
induction seen in experiments 1 and 2, respectively. Abbreviations are
as in Fig. 1.
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TABLE 1.
Classification of changes in CEF gene expression
following infection with the very virulent RB1B strain of MDV
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Inconsistency among array experiments makes replication of results
essential for studies of MDV. This inconsistency is not
unexpected
given the complexities and limitations of the MDV system.
First, there
are no cell lines for propagation of MDV, and the
virus is generally
grown in primary or secondary CEF. Therefore,
it is not possible to
synchronize infections to the degree that
would be easily achieved with
other viruses. We chose 2 and 4
dpi as the times to sample, as these
represent a relatively early
point in the infection before cytopathic
effects are apparent
and a relatively late time in the infection when
plaques are visible.
Second, MDV is a cell-associated virus and
therefore cannot be
used at high multiplicities of infection. We infect
as heavily
as possible (10
5 infected cells/1.2 × 10
7 uninfected CEF), but only a fraction of the cells
plated eventually
become infected. This means that a large portion of
the mRNA being
purified at the time of harvest is from uninfected
cells, which
probably obscures the true magnitude of any differences
observed.
One must keep in mind that differences seen are the result of
mRNA levels both in infected cells and in uninfected cells also
present
in the
culture.
Northern hybridizations were used to confirm gene expression changes
first observed on microarrays for selected genes (Fig.
3). Poly(A)
+ RNA (1 µg)
purified from uninfected CEF or RB1B-infected CEF
was electrophoresed,
blotted, and probed using riboprobes transcribed
by T7 RNA polymerase
off of
NotI-linearized cDNA clones. mRNA
levels were
elevated at 1 dpi for MHC class I and at 2 dpi for
MIP,
quiescence-specific protein, and
2-microglobulin. The
RNA
preparations used for Northern analysis were different from those
used for microarrays and therefore reflect variation in the timing
of
the infection at harvest. Nevertheless, induced levels of these
species
were apparent qualitatively.
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FIG. 3.
Northern analysis of poly(A)+ RNA purified
from CEF that were either uninfected or infected with RB1B. Probes
(shown at the right) consisted of riboprobes transcribed by T7 RNA
polymerase off of NotI-linearized cDNA clones. RNA was
harvested at 1 dpi for MHC class I and at 2 dpi for all other
samples.
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Host genes reproducibly induced upon infection of CEF with MDV can be
grouped into those involved in inflammation and cellular
stress (MIP
and clusterin), cell growth and differentiation (quiescence-specific
protein, TSA-1, and IL-13R), antigen presentation (MHC class I,
MHC
class II, and
2-microglobulin), and IFN responses (IRF-1
and IFN-inducible protein). Species that did not fall obviously
into
these classes were ALV-J, a serine/threonine kinase, and
ovotransferrin.
MIP induction in these and other experiments was strong and striking, a
result that is not surprising given that MDV infection
is expected to
induce an inflammatory response. MIP-1
is a small,
inducible
cytokine that belongs to the C-C chemokine subfamily
(
9).
MIP-1
has proinflammatory activities and also inhibits
growth of
hematopoietic stem cells (
9). Null mice that lack
MIP-1
are hematopoietically normal but resist coxsackievirus-induced
myocarditis and show decreased pneumonitis and delayed viral clearance
following exposure to influenza virus (
10). Thus, MIP-1
appears
to mediate inflammatory responses during viral
infection.
With regard to herpesvirus infections, MIP-1
plays a key role
in the development of herpetic stromal keratitis, a blinding
inflammatory condition that develops in mice infected with
replication-competent
herpes simplex virus (
42,
48). The
Kaposi's sarcoma-associated
herpesvirus genome encodes MIP-related
chemokine homologs, namely,
vMIP-I, vMIP-II, and vMIP-III (
3,
13). vMIP-I may affect
the Th1/Th2 balance during host immune
responses by antagonizing
C-C chemokine receptor 8 (CCR8), a receptor
expressed on Th2 T
cells. vMIP-II has been shown to activate and
attract human eosinophils
via CCR3. vMIP-III has not been
functionally characterized. It
is possible that MIP induction following
MDV infection is important
for T-cell attraction and infiltration at
the site of infection.
Calnek (
4) has pointed out that in
the case of MD, local T-cell
immune responses may contribute
significantly to disease, as they
provide targets for latent infection
and subsequent
transformation.
Another induced species likely to be related to inflammation and/or
cellular damage is clusterin (
29). Clusterin is a
conserved
glycoprotein, also known as apolipoprotein J, whose
expression
is increased in many cell types in response to stress.
Clusterin
has been reported to have chaperonin-like activity
(
22) and
anti-inflammatory activity (
32), and
it is expressed during
tissue differentiation and remodeling involving
apoptosis (
26,
29).
Quiescence-specific protein is a 20-kDa protein reported to be
present in contact-inhibited CEF (
2,
30). Factors that
induce quiescence, such as serum starvation and hydroxyurea
treatment,
induce this protein, whereas mitogen treatment reduces its
levels.
Transient expression assays have indicated that regulation of
quiescence-specific protein is, at least in part, at the
transcriptional
level. Induction of quiescence-specific gene
expression following
MDV infection suggests that viral infection
inhibits cellular
proliferation. This is consistent with the idea that
upon infection,
a herpesvirus poises cells to accumulate factors needed
for DNA
synthesis and simultaneously inhibits cell cycle progression
such
that the virus can exploit the replication-ready environment for
its own
benefit.
TSA-1 is a developmentally regulated
glycosylphosphatidylinositol-anchored differentiation antigen that
is identical to stem
cell antigen 2 (
33,
37). It plays a
key role in T-cell differentiation
by participating in T-cell
receptor/CD3-mediated apoptosis of
immature thymocytes
(
33). It also functions in T-cell activation
via the
T-cell receptor signaling pathway (
37). Our results
unexpectedly indicate that chicken TSA-1 is expressed in MDV-infected
fibroblasts. Since MDV latently infects and can transform T cells
in
vivo, the finding that infection induces a factor important
for T-cell
activation and differentiation is
provocative.
Human IL-13 is known to stimulate proliferation, differentiation, and
effector functions of B lymphocytes and macrophages
(
47).
IL-13 is closely related to IL-4 (
8). Receptors for
these
human interleukins have been characterized and compared
(
6). The IL-13 receptor has not been previously described
for
chickens.
Elevation of MHC class I, MHC class II, and
2-microglobulin mRNA levels was unexpected since many
viruses, including herpesviruses,
have been reported to down-regulate
cell surface expression of
species involved in antigen presentation,
particularly MHC class
I. For example, herpes simplex virus ICP47
associates with transporter
for antigen processing (TAP) in a
species-specific manner and
blocks peptide binding and subsequent
translocation of antigenic
peptides across the endoplasmic reticulum
(
15,
19,
31,
45).
Bovine herpesvirus 1 inhibits MHC class
I cell surface expression
by down-regulating TAP activity in bovine
epithelial cells, although
viral gene products involved are not known
(
20). HCMV uses several
mechanisms to interfere with
antigen presentation. TAP activity
continuously declines during HCMV
infection of fibroblasts (
18).
HCMV US3 binds
2-microglobulin-associated class I heavy chains,
making
them susceptible to destabilization mediated by both HCMV
US2 and US11
gene products (
25). Likewise, murine cytomegalovirus
m06
binds
2-microglobulin-associated class I molecules and
redirects
them for endocytosis (
36). HCMV US2 mediates
degradation of
two components of the MHC class II antigen presentation
pathway,
namely, DR
and DM
(
44).
Recent microscopy results suggest that MDV MHC class I expression is
actually down-regulated within individual infected CEF
but consistently
up-regulated in neighboring cells present in
the culture (J. Kent,
E. L. Bernberg, and R. W. Morgan, unpublished
data). Thus,
our microarray results reflected transcription changes
occurring in the
entire culture, one that contained a majority
of uninfected cells.
Up-regulation in neighboring cells may be
IFN mediated. Indeed, a
chicken fibroblast cell line, C32, stably
transfected to constitutively
overexpress IFN-1 showed enhanced
MHC class I surface antigen
expression (
50). Furthermore, elevation
of IRF-1
(
24) mRNA was consistently seen in the microarray
analyses.
IRF-1 is a highly conserved transcription factor that
mediates
responses to viral infections and IFNs. In CEF, IRF-1 is
strongly
induced by IFN
treatment.
Three other consistently induced species that are less well understood
are ALV-J, a serine/threonine kinase, and ovotransferrin.
It is likely
that ALV-J-specific hybridization in these experiments
was due to gene
expression from endogenous retroviruses related
to ALV-J. ALV-J is
currently a problematic chicken virus present
in flocks worldwide.
Serotype 2 MDV is known to augment ALV-induced
lymphoid leukosis in
some genetic lines of chickens (
1). In
addition, serotype
2 MDV has been reported to enhance ALV gene
expression and protein
accumulation in coinfected cell cultures
(
35).
Ovotransferrin (
23) is a key iron delivery and
iron-scavenging
protein. The chicken serine/threonine protein kinase
represents
a novel homolog, poorly understood at this
time.
In summary, we have used a microarray containing more than 1,000 selected, nonredundant chicken cDNAs to learn that MDV infection
of CEF
results in reproducible elevation of steady-state levels
of certain
cellular mRNAs. We have learned that genes involved
in virus-induced
inflammation and IFN responses appear consistently
induced. Even in
CEF, MDV infection appears to induce expression
of TSA-1, a gene
important for T-cell differentiation and activation.
These results
provide a powerful platform for additional studies
aimed at
understanding the biology of MDV. For example, similar
studies using
oncogenic strains with different pathogenicities,
nononcogenic and
vaccine strains of MDV, chicken tissues following
in vivo infections of
susceptible and resistant lines of chickens,
lymphoblastoid cell lines,
and tumors promise to be revealing
and are in
progress.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Animal and Food Sciences, Townsend Hall, University of Delaware,
Newark, DE 19717-1303. Phone: (302) 831-1341. Fax: (302) 831-2822. E-mail: morgan{at}udel.edu.
| |
REFERENCES |
| 1.
|
Bacon, L. D.,
R. L. Witter, and A. M. Fadly.
1989.
Augmentation of retrovirus-induced lymphoid leukosis by Marek's disease herpesviruses in white leghorn chickens.
J. Virol.
63:504-512[Abstract/Free Full Text].
|
| 2.
|
Bedard, P. A.,
Y. Yannoni,
D. L. Simmons, and R. L. Erikson.
1989.
Rapid repression of quiescence-specific gene expression by epidermal growth factor, insulin, and pp60v-src.
Mol. Cell. Biol.
9:1371-1375[Abstract/Free Full Text].
|
| 3.
|
Boshoff, C.,
Y. Endo,
P. D. Collins,
Y. Takeuchi,
J. D. Reeves,
V. L. Schweickart,
M. A. Siani,
T. Sasaki,
T. J. Williams,
P. W. Gray,
P. S. Moore,
Y. Chang, and R. A. Weiss.
1997.
Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines.
Science
278:290-294[Abstract/Free Full Text].
|
| 4.
|
Calnek, B. W.
1986.
Marek's disease a model for herpesvirus oncology.
Crit. Rev. Microbiol.
12:293-320[Medline].
|
| 5.
|
Calnek, B. W., and R. L. Witter.
1997.
Marek's disease, p. 369-413.
In
B. W. Calnek (ed.), Diseases of poultry, 10th ed. Iowa State University Press, Ames, Iowa.
|
| 6.
|
Caput, D.,
P. Laurent,
M. Kaghad,
J. M. Lelias,
S. Lefort,
N. Vita, and P. Ferrara.
1996.
Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor alpha chain.
J. Biol. Chem.
271:16921-16926[Abstract/Free Full Text].
|
| 7.
|
Chambers, J.,
A. Angulo,
D. Amaratunga,
H. Guo,
Y. Jiang,
J. Wan,
A. Bittner,
K. Frueh,
M. Jackson,
P. Peterson,
M. Erlander, and P. Ghazal.
1999.
DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression.
J. Virol.
73:5757-5766[Abstract/Free Full Text].
|
| 8.
|
Chomarat, P., and J. Banchereau.
1998.
Interleukin-4 and interleukin-13: their similarities and discrepancies.
Int. Rev. Immunol.
17:1-52[Medline].
|
| 9.
|
Cook, D. N.
1996.
The role of MIP-1 alpha in inflammation and hematopoiesis.
J. Leukoc. Biol.
59:61-66[Abstract].
|
| 10.
|
Cook, D. N.,
M. A. Beck,
T. M. Coffman,
S. L. Kirby,
J. F. Sheridan,
I. B. Pragnell, and O. Smithies.
1995.
Requirement of MIP-1 alpha for an inflammatory response to viral infection.
Science
269:1583-1585[Abstract/Free Full Text].
|
| 11.
|
DeRisi, J. L.,
V. R. Iyer, and P. O. Brown.
1997.
Exploring the metabolic and genetic control of gene expression on a genomic scale.
Science
278:680-686[Abstract/Free Full Text].
|
| 12.
|
DeRisi, J. L.,
L. Penland,
P. O. Brown,
M. L. Bittner,
P. S. Meltzer,
M. Ray,
Y. Chen,
Y. A. Su, and J. M. Trent.
1996.
Use of a cDNA microarray to analyze gene expression patterns in human cancer.
Nat. Genet.
14:457-460[CrossRef][Medline].
|
| 13.
|
Endres, M. J.,
C. G. Garlisi,
H. Xiao,
L. Shan, and J. A. Hedrick.
1999.
The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8.
J. Exp. Med.
189:1993-1998[Abstract/Free Full Text].
|
| 14.
|
Fambrough, D.,
D. McClure,
A. Kazlauskas, and E. S. Lander.
1999.
Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes.
Cell
97:727-741[CrossRef][Medline].
|
| 15.
|
Fruh, K.,
K. Ahn,
H. Djaballah,
P. Sempe,
P. M. Van Endert,
R. Tampe,
P. A. Peterson, and Y. Yang.
1995.
A viral inhibitor of peptide transporters for antigen presentation.
Nature
375:415-418[CrossRef][Medline].
|
| 16.
|
Gray, N. S.,
L. Wodicka,
A.-M. Thunnissen,
T. C. Norman,
S. Kwon,
F. H. Espinoza,
D. O. Morgan,
G. Barnes,
S. LeClerc,
L. Meijer, et al.
1998.
Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.
Science
281:533-538[Abstract/Free Full Text].
|
| 17.
|
Heller, R. A.,
M. Schena,
A. Chai,
D. Shalon,
T. Bedoin,
J. Gilmore,
D. E. Woolley, and R. W. Davis.
1997.
Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.
Proc. Natl. Acad. Sci. USA
94:2150-2155[Abstract/Free Full Text].
|
| 18.
|
Hengel, H.,
T. Flohr,
G. J. Hammerling,
U. H. Koszinowski, and F. Momburg.
1996.
Human cytomegalovirus inhibits peptide translocation into the endoplasmic reticulum for MHC class I assembly.
J. Gen. Virol.
77:2287-2296[Abstract/Free Full Text].
|
| 19.
|
Hill, A.,
P. Jugovic,
I. York,
G. Russ,
J. Bennink,
J. Yewdell,
H. Ploegh, and D. Johnson.
1995.
Herpes simplex virus turns off the TAP to evade host immunity.
Nature
375:411-415[CrossRef][Medline].
|
| 20.
|
Hinkley, S.,
A. B. Hill, and S. Srikumaran.
1998.
Bovine herpesvirus-1 infection affects the peptide transport activity in bovine cells.
Virus Res.
53:91-96[CrossRef][Medline].
|
| 21.
|
Holstege, F. C.,
E. G. Jennings,
J. J. Wyrick,
T. I. Lee,
C. J. Hengartner,
M. R. Green,
T. R. Golub,
E. S. Lander, and R. A. Young.
1998.
Dissecting the regulatory circuitry of a eukaryotic genome.
Cell
95:717-728[CrossRef][Medline].
|
| 22.
|
Humphreys, D. T.,
J. A. Carver,
S. B. Easterbrook-Smith, and M. R. Wilson.
1999.
Clusterin has chaperone-like activity similar to that of small heat shock proteins J.
Biol. Chem.
274:6875-6881[Abstract/Free Full Text].
|
| 23.
|
Jeltsch, J., and P. Chambon.
1982.
The complete nucleotide sequence of chicken ovotransferrin mRNA.
Eur. J. Biochem.
122:291-295[Medline].
|
| 24.
|
Jingwirth, C.,
M. Rebbert,
K. Ozato,
H. J. Degen,
U. Schultz, and I. B. Dawid.
1995.
Chicken interferon consensus sequence-binding protein (ICSBP) and interferon regulatory factor (IRF) 1 genes reveal evolutionary conservation in the IRF gene family.
Proc. Natl. Acad. Sci. USA
92:3105-3109[Abstract/Free Full Text].
|
| 25.
|
Jones, T. R., and L. Sun.
1997.
Human cytomegalovirus US2 destabilizes major histocompatibility complex class I heavy chains.
J. Virol.
71:2970-2979[Abstract].
|
| 26.
|
Klock, G.,
S. Storch,
J. Rickert,
C. Gutacker, and C. Koch-Brandt.
1998.
Differential regulation of the clusterin gene by Ha-ras and c-myc oncogenes and during apoptosis.
J. Cell. Physiol.
177:593-605[CrossRef][Medline].
|
| 27.
|
Lashkari, D. A.,
J. L. DeRisi,
J. H. McCusker,
A. F. Namath,
C. Gentile,
S. Y. Hwang,
P. O. Brown, and R. W. Davis.
1997.
Yeast microarrays for genome wide parallel genetic and gene expression analysis.
Proc. Natl. Acad. Sci. USA
94:13057-13062[Abstract/Free Full Text].
|
| 28.
|
Madhani, H. D.,
T. Galitski,
E. S. Lander, and G. R. Fink.
1999.
Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signaling mutants.
Proc. Natl. Acad. Sci. USA
96:12530-12535[Abstract/Free Full Text].
|
| 29.
|
Mahon, M. G.,
K. A. Lindstedt,
M. Hermann,
J. Nimpf, and W. J. Schneider.
1999.
Multiple involvement of clusterin in chicken ovarian follicle development. Binding to two oocyte-specific members of the low density lipoprotein receptor gene family.
J. Biol. Chem.
274:4036-4044[Abstract/Free Full Text].
|
| 30.
|
Mao, P. L.,
M. Beauchemin, and P. A. Bedard.
1993.
Quiescence-dependent activation of the p20K promoter in growth-arrested chicken embryo fibroblasts.
J. Biol. Chem.
268:8131-8139[Abstract/Free Full Text].
|
| 31.
|
Neumann, L.,
W. Kraas,
S. Uebel,
G. Jung, and R. Tampe.
1997.
The active domain of the herpes simplex virus protein ICP47: a potent inhibitor of the transporter associated with antigen processing.
J. Mol. Biol.
272:484-492[CrossRef][Medline].
|
| 32.
|
Newkirk, M. M.,
P. Apostolakos,
C. Neville, and P. R. Fortin.
1999.
Systemic lupus erythematosus, a disease associated with low levels of clusterin/apoJ, an antiinflammatory protein.
J. Rheumatol.
26:597-603[Medline].
|
| 33.
|
Noda, S.,
A. Kosugi,
S. Saitoh,
S. Narumiya, and T. Hamaoka.
1996.
Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2.
J. Exp. Med.
183:2355-2360[Abstract/Free Full Text].
|
| 34.
|
Perou, C. M.,
S. S. Jeffrey,
M. Van de Rijn,
C. A. Rees,
M. B. Eisen,
D. T. Ross,
A. Pergamenschikov,
C. F. Williams,
S. X. Zhu,
J. C. F. Lee,
D. Lashkari,
D. Shalon,
P. O. Brown, and D. Botstein.
1999.
Distinctive gene expression patterns in human mammary epithelial cells and breast cancers.
Proc. Natl. Acad. Sci. USA
96:9212-9217[Abstract/Free Full Text].
|
| 35.
|
Pulaski, J. T.,
V. L. Tieber, and P. M. Coussens.
1992.
Marek's disease virus-mediated enhancement of avian leukosis virus gene expression and virus production.
Virology
186:113-121[CrossRef][Medline].
|
| 36.
|
Reusch, U.,
W. Muranyi,
P. Lucin,
H. G. Burgert,
H. Hengel, and U. H. Koszinowski.
1999.
A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation.
EMBO J.
15:1081-1091[CrossRef].
|
| 37.
|
Saitoh, S.,
A. Kosugi,
S. Noda,
N. Yamamoto,
M. Ogata,
Y. Minami,
K. Miyake, and T. Hamaoka.
1995.
Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-1 (Sca-2).
J. Immunol.
155:5574-5581[Abstract].
|
| 38.
|
Schena, M.,
D. Shalon,
R. W. Davis, and P. O. Brown.
1995.
Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
Science
270:467-470[Abstract/Free Full Text].
|
| 39.
|
Shalon, D.,
S. Smith, and P. O. Brown.
1996.
A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization.
Genome Res.
6:639-645[Abstract/Free Full Text].
|
| 40.
|
Tamayo, P.,
D. Slonim,
J. Mesirov,
Q. Zhu,
S. Kitareewan,
E. Dmitrovsky,
E. S. Lander, and T. R. Golub.
1999.
Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation.
Proc. Natl. Acad. Sci. USA
96:2907-2912[Abstract/Free Full Text].
|
| 41.
|
Teague, T. K.,
D. Hildeman,
R. M. Kedl,
T. Mitchell,
W. Rees,
B. C. Schaefer,
J. Bender,
J. Kappler, and P. Marrack.
1999.
Activation changes the spectrum but not the diversity of genes expressed by T cells.
Proc. Natl. Acad. Sci. USA
96:12691-12696[Abstract/Free Full Text].
|
| 42.
|
Thomas, J.,
S. Kanangat, and B. T. Rouse.
1998.
Herpes simplex virus replication-induced expression of chemokines and proinflammatory cytokines in the eye: implications in herpetic stromal keratitis.
J. Interferon Cytokine Res.
18:681-690[Medline].
|
| 43.
|
Tirunagaru, V. G.,
L. Sofer,
J. Cui, and J. Burnside.
2000.
An expressed sequence tag database of T-cell-enriched activated chicken splenocytes: sequence analysis of 5251 clones.
Genomics
66:144-151[CrossRef][Medline].
|
| 44.
|
Tomazin, R.,
J. Boname,
N. R. Hegde,
D. M. Lewinsohn,
Y. Altschuler,
T. R. Jones,
P. Cresswell,
J. A. Nelson,
S. R. Riddell, and D. C. Johnson.
1999.
Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells.
Nat. Med.
5:1039-1043[CrossRef][Medline].
|
| 45.
|
Tomazin, R.,
N. E. Van Schoot,
K. Goldsmith,
P. Jugovic,
P. Sempe,
K. Fruh, and D. C. Johnson.
1998.
Herpes simplex virus type 2 ICP47 inhibits human TAP but not mouse TAP.
J. Virol.
72:2560-2563[Abstract/Free Full Text].
|
| 46.
|
Trent, J. M.,
M. Bittner,
J. Zhang,
R. Wiltshire,
M. Ray,
Y. Su,
E. Garcia,
P. Meltzer,
J. DeRisi,
L. Penland, and P. Brown.
1997.
Use of microgenomic technology for analysis of alterations in DNA copy number and gene expression in malignant melanoma.
Clin. Exp. Immunol.
107(Suppl. 1):33-40.
|
| 47.
|
Trigona, W. L.,
A. Hirano,
W. C. Brown, and D. M. Estes.
1999.
Immunoregulatory roles of interleukin-13 in cattle.
J. Interferon Cytokine Res.
19:1317-1324[CrossRef][Medline].
|
| 48.
|
Tumpey, T. M.,
H. Cheng,
D. N. Cook,
O. Smithies,
J. E. Oakes, and R. N. Lausch.
1998.
Absence of macrophage inflammatory protein 1 alpha prevents the development of blinding herpes stromal keratitis.
J. Virol.
72:3705-3710[Abstract/Free Full Text].
|
| 49.
|
Zhu, H.,
J.-P. Cong,
G. Mamtora,
T. Gingeras, and T. Shenk.
1998.
Cellular gene expression altered by human cytomegalovirus: global monitoring with oligonucleotide arrays.
Proc. Natl. Acad. Sci. USA
95:14470-14475[Abstract/Free Full Text].
|
| 50.
|
Zoeller, B.,
M. Popp,
A. Walter,
I. Redmann-Muller,
E. Lodemann, and C. Jungwirth.
1998.
Overexpression of chicken interferon regulatory factor-1 (CH-IRF-1) induces constitutive expression of MHC class I antigens but does not confer virus resistance to a permanent chicken fibroblast cell line.
Gene
222:269-278[CrossRef][Medline].
|
Journal of Virology, January 2001, p. 533-539, Vol. 75, No. 1
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.1.533-539.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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