Previous Article | Next Article 
J Virol, January 1998, p. 767-771, Vol. 72, No. 1
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Molecular and Immunophenotypical Characterization
of a Feline Immunodeficiency Virus (FIV)-Associated Lymphoma: a
Direct Role for FIV in B-Lymphocyte Transformation?
Julia A.
Beatty,1,*
John J.
Callanan,2,
Anne
Terry,1
Oswald
Jarrett,1 and
James C.
Neil1
Department of Veterinary Pathology,
University of Glasgow, Bearsden, Glasgow G61 1QH, United
Kingdom,1 and
Department of Agriculture
and Food, Regional Veterinary Laboratory, Bishopstown, Cork,
Ireland2
Received 30 June 1997/Accepted 19 September 1997
 |
ABSTRACT |
We describe the histopathological, immunohistochemical, and
molecular characterization of a lymphoma arising in a 7-year-old cat
following experimental infection with feline immunodeficiency virus
(FIV). The tumor was high grade and of B-cell lineage. The transformed
cell had an immature phenotype (CD79a+,
CD79b
, CD21, immunoglobulin heavy and light
chain negative), confirmed by antigen receptor gene analysis, which
showed germ line configuration. Single-copy, clonally integrated FIV
provirus was detected in tumor genomic DNA. FIV p24 antigen was not
detected in tumor cells by immunostaining. This study provides the
first evidence that the feline lentivirus may play a direct role in
cell transformation under certain circumstances.
| |
TEXT |
Lymphoma (lymphosarcoma) is the most
common tumor in cats (19). Feline leukemia virus is the
etiological agent of the majority of these tumors, especially in
younger cats, but lymphoma can occur independently of feline leukemia
virus infection (25). Recently, epidemiological studies have
described lymphoproliferative malignancies in association with the
feline lentivirus feline immunodeficiency virus (FIV) (1, 4, 5, 8,
23, 24, 40, 43, 44, 47), and an increased risk of lymphoma in FIV-infected cats has been demonstrated (15, 23, 45, 46).
Several common features have emerged from the examination of
FIV-associated lymphomas. These lymphomas are predominantly extranodal, conforming to the least common anatomical classification of
miscellaneous (7, 13, 23, 40). Where histological and
immunophenotypical analyses have been carried out, the tumors have been
found to be of B-cell lineage (7, 13, 40) and usually of the
high-grade immunoblastic or centroblastic type (7).
FIV-associated lymphomas thus resemble those seen in human
immunodeficiency virus type 1 (HIV-1) infection of humans (21,
30) and in simian immunodeficiency virus infection of nonhuman
primates (16, 41).
In contrast to the directly oncogenic retroviruses such as the murine
and feline leukemia viruses, lentiviruses are generally considered to
play an indirect role in tumor development. Most HIV-1-associated
lymphomas are believed to develop secondary to one or a combination of
factors, including immunodeficiency (38), polyclonal B-cell
activation (34), and the involvement of other infectious
agents, notably Epstein-Barr virus (14, 18). However, a
direct causal role is implied for HIV-1 in a T-cell lymphoma in which
an integrated provirus was demonstrated (22, 48).
The role of FIV in tumorigenesis is unknown, but the lack of integrated
sequences in the small number of tumors examined by restriction
fragment analysis to date has led to the provisional hypothesis that
the virus facilitates tumor development by indirect mechanisms similar
to those postulated for HIV-1 (50). In contrast, we have now
detected FIV sequences in DNA extracted from another lymphoma, this one
occurring in a cat experimentally infected with FIV. This tumor
consisted of a clonal precursor B-cell population. Further analysis
demonstrated a single integration site, indicating that viral infection
occurred prior to clonal expansion. This work suggests that a
lentivirus may be directly involved in B-cell transformation.
Histopathological and immunophenotypical characterization of the
tumor.
A 10-month-old neutered male specific-pathogen-free cat was
inoculated with FIV Glasgow-8 as part of a long-term pathogenesis study
(9). Six years 3 months after infection, a preliminary diagnosis of neoplastic disease was made and euthanasia was carried out. For histopathological examination, tissues were preserved by
fixation in 10% neutral buffered formalin, embedded in paraffin, cut
into 5-µm-thick sections, and stained with hematoxylin and eosin.
Selected sections were also stained with Giemsa stain. Microscopic
examination confirmed the presence of tumor tissue in the liver, lymph
nodes, and omentum. This tumor was composed of mononuclear cells with
medium to large nuclei. The majority of cells had oval, cleaved, or
indented nuclei with two or three small nucleoli. These cells resembled
centroblasts. A smaller number of cells (<10%) had larger nuclei with
a prominent, centrally located, large nucleolus. Some of these cells
had prominent, intensely basophilic cytoplasm and resembled
immunoblasts. The remainder had weakly staining or no cytoplasm and
resembled paraimmunoblasts. By use of the updated Kiel classification
system (29), this tumor was classified as high grade and of
the monomorphic centroblastic subtype. Cells were arranged in sheets to
form nodules within liver tissue and lymph nodes. Nodules in the liver
were separated by compressed residual hepatic parenchyma which
contained vacuolated hepatocytes. Nodules within lymph nodes were
located in the cortex and coalesced or were separated by preexisting
trabecular tissue. Medullary tissue was compressed. Neoplastic cells
were present in a fine fibrous stroma, and numerous foci of necrosis,
often in association with inflammatory cells, were observed.
Aggregations of small lymphocytes were present both within nodules and
at their edges, and irregular infiltrates of macrophages were also
observed at the perimeter of many nodules. Mitotic figures, many of
bizarre shapes, were frequently noted, and hyperchromatic nuclei were also present. Bone marrow was not infiltrated by the tumor.
To investigate the tumor cell phenotype, we carried out immunostaining
of paraffin-embedded sections and cryostat sections as described in a
previous study with the following panel of antibodies: anti-CD79a
(mb-1), anti-CD79b (B29), anti-CD21, anti-immunoglobulin G (IgG),
anti-IgM, anti-IgA, anti-
light chain, anti-
light chain,
anti-CD3, anti-CD4, anti-CD5, anti-CD8, anti-major histocompatibility complex class II (MHCII), anti-bcl-2, and MAC387 (7). Normal feline lymphoid tissue stained with anti-CD4 or anti-CD8 antibodies was
used as a positive control. The primary antibody was omitted to provide
negative controls.
The neoplastic cells expressed the B-cell marker CD79a (Fig.
1) and were negative for all other
markers tested (data not shown).
The majority of small lymphocytes
characterized as T-cell infiltrates
expressed CD3, with smaller numbers
of the population also expressing
CD8 and CD5. The presence of
macrophages was confirmed by use
of MAC387 antibodies, and a proportion
of infiltrating small lymphocytes
were characterized as B cells by
their expression of either IgG
or IgA heavy chains and
or
light
chains.
View larger version (150K):
[in this window]
[in a new window]
|
FIG. 1.
Anti-CD79a staining of neoplastic cells. Formalin-fixed,
paraffin-embedded tissue sections were stained by the avidin-biotin
complex technique, nickel enhancement, and a safranin (pink)
counterstain. CD79a-positive tumor cells, which stain darkly, are
visible invading the lymph node cortex. Bar, 20 µm. Objective,
40×.
|
|
The antibody used to stain CD79a labels B cells from several mammalian
species (
31), including domestic cats (
7,
32).
CD79a is expressed at a very early stage in B-cell differentiation,
prior to immunoglobulin heavy chain [Ig(H)] constant region µ-chain
gene rearrangement and CD79b expression, and may persist until
the
plasma cell stage (
3,
26,
31,
32,
51). The finding
that
tumor cells were negative for other B-cell markers, i.e.,
CD79b,
CD21, and surface immunoglobulin heavy and light chains,
suggests
that malignant transformation occurred at a differentiation
stage
earlier than the pre-B-cell stage, i.e., at the pro-B-cell
or stem cell
stage, in rodent models (
20,
49). CD21-positive
B cells form
an important productive reservoir of FIV infection
in vivo
(
12). Our results extend these observations by demonstrating
that B cells can be infected in vivo at a very early stage of
development. These combined investigations established that the
tumor
was a high-grade, extranodal lymphoma with B-cell characteristics,
typical of those described previously in association with FIV
infection
(
7,
40).
Genotypic characterization.
To investigate the clonality and
lineage of this lymphoma, antigen receptor gene arrangements were
investigated by Southern blot analysis. Genomic DNA was obtained from
snap-frozen tumor tissue, autologous salivary gland, and FIV-infected
cell line FL4 (52) by the use of standard phenol-chloroform
extraction and ethanol precipitation. Southern blot hybridization
analysis of HincII- and HindIII-digested
high-molecular-weight DNA was performed as described previously
(35, 50). The status of the genes encoding the
T-cell-receptor 
-chain and the Ig(H) constant region was determined
by use of a C probe (FeTCRC) with HincII-digested DNA
and a Cµ probe (FeCµ) with HindIII-digested DNA,
respectively (50). Probes were radiolabelled to a high
specific activity with 32P by random priming.
Autoradiographs were developed for 1 to 4 days at 
70°C. With this
technique, rearranged antigen receptor genes in clonal T- or B-cell
populations gave different germ line patterns of hybridizing fragments.
We found that, in each digest, DNA from the tumor, salivary gland, and
FL4 cells generated identical restriction fragments (Fig.
2). The sizes of the observed fragments, i.e., 9, 3, and 8 kb, representing FeTCRC1, FeTCRC2, and FeCµ, respectively, are consistent with previously published data for the
feline germ line (50). This result corroborates the findings of the phenotypical analysis, which showed that the neoplastic cell had
characteristics of an early B cell, by indicating that antigen receptor
rearrangement had not occurred prior to transformation.
View larger version (64K):
[in this window]
[in a new window]
|
FIG. 2.
Analysis of antigen receptor gene configuration. Tumor
(T), autologous salivary gland control (C), and FL4 (P) DNAs were
digested with HincII and probed with FeTCRC (A) or
digested with HindIII and probed with FeCµ (B) to
determine the status of the genes encoding the T-cell-receptor
-chain and Ig(H) constant regions, respectively. The three DNA
samples gave identical germ line patterns. Lane M contains molecular
size standards (sizes, in kilobases, are on the left).
|
|
Clonal integration of FIV proviral sequences.
To determine
whether FIV might be involved directly in lymphomagenesis, we carried
out Southern blot analysis to look for FIV sequences in tumor DNA, as
described previously (35, 50). DNAs prepared from autologous
salivary gland and from FL4 cells were used as controls.
PvuII-digested DNA was probed with a FIV-specific probe
consisting of a 1.2-kb FIV Glasgow-14 (42)
gag-pol fragment (1,242 to 2,431 bp from the 5' end of the
genome) and a 1.3-kb FIV Petaluma 34TF10 (39) env
fragment (6,978 to 8,090 bp from the 5' end of the genome). Filters
were washed under high-stringency conditions (0.1% SSC [1× SSC is
0.15 M NaCl plus 0.015 M sodium citrate]-0.5% sodium dodecyl
sulfate). Two hybridizing bands were detected in the tumor tissue but
were absent from the autologous control tissue (Fig.
3), demonstrating the presence of
significant levels of tumor-specific FIV DNA.
View larger version (72K):
[in this window]
[in a new window]
|
FIG. 3.
Detection of FIV sequence in an FIV-associated lymphoma.
Tumor (T), autologous salivary gland control (C), and FIV-infected FL4
cells (P) were analyzed by Southern blotting. DNA from these tissues
was digested with PvuII and probed with a mixed FIV
gag-pol/env probe. FIV DNA was detected as two hybridizing
bands (arrows) in tumor DNA but not in salivary gland DNA. Lane M
contains molecular size standards (sizes, in kilobases, are on the
left).
|
|
To determine the integration status of the FIV DNA in tumor tissue, the
technique was modified to analyze undigested genomic
DNA as follows.
High-molecular-weight DNA was run on a 0.6% agarose
gel and
transferred to a charged nylon filter (Hybond-N+; Amersham
International, Amersham, United Kingdom). The filter was neutralized
in
0.5 M Tris (pH 7.0) for 5 min and then probed and washed as
described
above. The hybridizing sequence comigrated with the
bulk of the
undigested DNA (Fig.
4), indicating that
the FIV DNA
was present as a high-molecular-weight complex or as
integrated
proviral sequences.
View larger version (98K):
[in this window]
[in a new window]
|
FIG. 4.
Determination of the integration status of FIV DNA
sequence in tumor DNA. Undigested tumor (T), autologous salivary gland
control (C), and FL4 (P) DNAs were probed with a mixed FIV
gag-pol/env probe on a Southern blot. FIV DNA comigrates
with tumor genomic DNA (arrow). Lane M contains molecular size
standards (sizes, in kilobases, are on the left).
|
|
The status of these sequences was investigated further by digestion of
tumor cell and control DNA with
EcoRI, which does not
cut
within the provirus of the inoculum strain, FIV Glasgow-8,
and with
SstI, which recognizes a single site in the provirus,
and
analyzed with the FIV probe as described above. The
SstI
site
in FIV Glasgow-8 is located approximately 500 bp downstream of
the
5' long terminal repeat, proximal to
gag, and therefore does
not interfere with hybridization of the probe. Digestion with
these
enzymes should therefore generate one fragment per integration
site if
the FIV sequences in the tumor cell DNA retain the structure
of the
infecting virus. A single, intense hybridizing band was
seen at 11.5 and 21 kb in the
EcoRI and
SstI digests,
respectively
(Fig.
5), indicating
monoclonal integration of FIV provirus in
tumor cell DNA.
View larger version (68K):
[in this window]
[in a new window]
|
FIG. 5.
Demonstration of monoclonal integration of FIV provirus
in tumor DNA Tumor (T), autologous salivary gland control (C), and FL4
(P) DNAs were digested with EcoRI (A), which does not
recognize a site within FIV provirus, or with SstI (B),
which cuts once in FIV provirus, and probed with a mixed FIV
gag-pol/env probe. A single sharp band in both digests (11.5 [A] and 21 [B] kb) indicates monoclonal integration of FIV provirus
in tumor tissue. The presence of fragments smaller than the virus
genome (9 kb) in the FL4 EcoRI digest has been observed
consistently (50) and may represent the integration of
incomplete proviral genomes and the presence of partial unintegrated
sequences. Lane M contains molecular size standards (sizes, in
kilobases, are on the left).
|
|
Investigation of FIV core antigen expression in tumor cells.
We used immunocytochemical staining to determine whether the FIV capsid
protein, p24, was expressed in tumor cells. Cells were dried onto
flat-bottom, 96-well plates (5 × 104 cells/well) by
incubation at 37°C overnight and then fixed and stained with an
anti-p24 monoclonal antibody (Serotec Ltd., Oxford, United Kingdom) as
described previously (37). FL4 cells and the uninfected
feline lymphoid cell line MYA-1 (33) served as positive and
negative controls, respectively. While FL4 cells were strongly positive
and MYA-1 cells were negative for FIV p24 antigen, we could not detect
FIV p24 antigen expression in tumor cells (data not shown). This result
suggests that the integrated provirus is not expressed in the tumor
cells but does not exclude the possibility of a transcriptionally
active but defective provirus.
Concluding remarks.
The most significant finding of this study
is the demonstration of a monoclonally integrated FIV provirus in tumor
DNA. This observation indicates that a single infection event preceded
clonal expansion of the transformed cell and raises the possibility of a direct oncogenic role for FIV.
Although a direct role has been postulated for HIV-1 in the initiation
of B-cell lymphoma and the results of some studies
(
2,
17),
including the demonstration that HIV-1 has transforming
properties in
vitro (
28), are consistent with this theory, Southern
blot
analysis of lymphoma tissue has to date failed to lend support.
In
contrast, a single-copy clonally integrated HIV-1 provirus
was
identified by Herndier and colleagues in a rare HIV-1-associated
T-cell
lymphoma (
22).
At this stage, we can only speculate as to the mechanism(s) by which
FIV may have contributed to cell transformation in this
case. Important
in this regard is the observation that viral gene
expression could not
be detected in tumor cells. This result suggests
that, while FIV may be
involved in an early lymphomagenic event,
viral gene expression is not
necessary to maintain the transformed
phenotype. Based on our findings,
FIV has features in common with
the human T-cell leukemia virus-bovine
leukemia virus group, which
typically induces tumors with clonally
integrated but transcriptionally
inactive provirus (
6,
10).
The favored explanation for the
oncogenic action of the human T-cell
leukemia virus-bovine leukemia
virus group is an
initiation-progression model in which early
expression of a viral
oncoprotein, Tax, induces cellular proliferation
but expression is lost
in malignant cells where secondary mutations
fix the transformed
phenotype (
11,
36).
Alternatively, a transcriptionally active, defective FIV provirus might
be acting as an insertional mutagen analogous to the
type C
retroviruses (
27) and as postulated for HIV-1 integration
within
fur upstream of the
c-fes/fps
proto-oncogene (
48). Transduction
of a cellular oncogene has
never been shown for a lentivirus but
remains a theoretical possibility
in the light of the rapid clinical
course and aggressive nature of this
lymphoma. Further analysis
of virus transcription and the provirus
integration site should
help to distinguish between these possible
mechanisms.
Although we have demonstrated proviral integration in a single case of
FIV-associated lymphoma, only a relatively small number
of cases have
been analyzed at the molecular level to date (
50).
More
extensive analysis will be necessary to determine the frequency
with
which this occurs and its wider implications for lentiviral
oncogenesis.
| |
ACKNOWLEDGMENTS |
We thank I. A. P. McCandlish for assisting with the gross
pathology and the histopathology, D. Y. Mason for providing
antibodies to detect CD79b, CD5, and bcl-2, H. Thompson for helpful
discussion, J. McDonald for providing FIV probe DNA, and J. Cole and A. Jenkins for technical help.
This work was supported by a Veterinary Research Fellowship (no.
878166) awarded by the Wellcome Trust.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Veterinary Pathology, University of Glasgow, Bearsden Rd., Glasgow G61 1QH, United Kingdom. Phone: 141 339 8855. Fax: 141 330 5602. E-mail: J.Beatty{at}udcf.gla.ac.uk.
Present address: Department of Veterinary Pathology, University
College of Dublin, Faculty of Veterinary Medicine, Ballsbridge, Dublin
4, Ireland.
| |
REFERENCES |
| 1.
|
Alexander, R.,
W. F. Robinson,
J. N. Mills,
C. R. Sherry,
E. Sherard,
A. J. Paterson,
S. E. Shaw,
W. T. Clark, and T. Hollingsworth.
1989.
Isolation of feline immunodeficiency virus from three cats with lymphoma.
Aust. Vet. Pract.
19:93-97.
|
| 2.
|
Astrin, S. M.,
E. Schattner,
J. Laurence,
R. I. Lebman, and C. Rodriguez-Alfageme.
1992.
Does HIV infection of B lymphocytes initiate AIDS lymphoma? Detection by PCR of viral sequences in lymphoma tissue.
Curr. Top. Microbiol. Immunol.
182:399-407[Medline].
|
| 3.
|
Astsaturov, I. A.,
E. Matutes,
R. Morilla,
B. K. Seon,
D. Y. Mason,
N. Farahat, and D. Catovsky.
1996.
Differential expression of B29 (CD79b) and mb-1 (CD79a) proteins in acute lymphoblastic leukaemia.
Leukemia
10:769-773[Medline].
|
| 4.
|
Barr, M. C.,
M. T. Butt,
K. L. Anderson,
D. Lin,
T. F. Kelleher, and F. W. Scott.
1993.
Spinal lymphosarcoma and disseminated mastocytoma associated with feline immunodeficiency virus infection in a cat.
J. Am. Vet. Med. Assoc.
202:1978-1980[Medline].
|
| 5.
|
Buracco, P.,
R. Guglielmino,
O. Abate,
V. Bocchini,
E. Cornaglia,
D. B. DeNicola,
M. Cilli, and P. Ponzio.
1992.
Large granular lymphoma in a FIV-positive and FeLV-negative cat.
J. Small Anim. Pract.
33:279-284.
|
| 6.
|
Burny, A.,
L. Willems,
I. Callebaut,
E. Adam,
I. Cludts,
F. Dequiedt,
L. Droogmans,
C. Grimonpont,
P. Kerkhofs,
M. Mammerickx,
D. Portetelle,
A. Van Den Broeke, and R. Kettmann.
1994.
Bovine leukaemia virus: biology and mode of transformation, p. 213-234. In
A. Minson, J. Neil, and M. McCrae (ed.), Viruses and cancer.
University Press, Cambridge, United Kingdom.
|
| 7.
|
Callanan, J.,
B. A. Jones,
J. Irvine,
B. J. Willett,
I. A. P. McCandlish, and O. Jarrett.
1996.
Histologic classification and immunophenotype of lymphosarcomas in cats with naturally and experimentally acquired feline immunodeficiency virus infections.
Vet. Pathol.
33:264-272[Abstract].
|
| 8.
|
Callanan, J. J.,
I. A. P. McCandlish,
B. O'Neil,
C. Lawrence,
M. Rigby,
A. M. Pacitti, and O. Jarrett.
1992.
Lymphosarcoma in experimentally induced feline immunodeficiency virus infection.
Vet. Rec.
130:293-295[Abstract].
|
| 9.
|
Callanan, J. J.,
H. T. Thompson,
S. J. Toth,
B. O'Neil,
C. L. Lawrence,
B. Willett, and O. Jarrett.
1992.
Clinical and pathological findings in feline immunodeficiency virus experimental infection.
Vet. Immunol. Immunopathol.
35:3-14[Medline].
|
| 10.
|
Cann, A. J., and S. Y. Chen.
1996.
Human T-cell leukemia virus types I and II, p. 1849-1880. In
B. N. Fields, D. M. Knipe, P. M. Howley, R. M. Chanock, J. L. Melnick, T. P. Monath, B. Roizman, and S. E. Straus (ed.), Fields virology.
Lippincott-Raven, Philadelphia, Pa.
|
| 11.
|
Cullen, B. R.
1992.
Mechanism of action of regulatory proteins encoded by complex retroviruses.
Microbiol. Rev.
56:375-394[Abstract/Free Full Text].
|
| 12.
|
Dean, G. A.,
G. H. Reubel,
P. F. Moore, and N. C. Pedersen.
1996.
Proviral burden and infection kinetics of feline immunodeficiency virus in lymphocyte subsets of blood and lymph node.
J. Virol.
70:5165-5169[Abstract/Free Full Text].
|
| 13.
|
English, R. V.,
P. Nelson,
C. M. Johnson,
M. Nasisse,
W. A. Tompkins, and M. B. Tompkins.
1994.
Development of clinical disease in cats experimentally infected with feline immunodeficiency virus.
J. Infect. Dis.
170:543-552[Medline].
|
| 14.
|
Ernberg, I.
1986.
The role of Epstein-Barr virus in lymphomas of homosexual males.
Prog. Allergy
37:301-318[Medline].
|
| 15.
|
Feder, B. M., and A. I. Hurvitz.
1990.
Feline immunodeficiency virus infection in 100 cats and association with lymphoma.
Proc. Am. Coll. Vet. Intern. Med. Forum
8:1112.
|
| 16.
|
Feichtinger, H.,
P. Putkonen,
C. Parravicini,
S. Li,
E. E. Kaaya,
D. Bottiger,
G. Biberfeld, and P. Biberfeld.
1990.
Malignant lymphomas in cynomolgus monkeys infected with simian immunodeficiency virus.
Am. J. Pathol.
137:1311-1315[Abstract].
|
| 17.
|
Ford, R. J.,
A. Goodacre,
B. Bohannon, and L. Donehower.
1990.
Identification of human retrovirus(es) in lymphoma cells from AIDS patients.
AIDS Res. Hum. Retroviruses
6:142-143.
|
| 18.
|
Hamilton-Dutoit, S. J.,
G. Pallesen,
M. B. Franzmann,
J. Karkov,
F. Black,
P. Skinhoj, and C. Pedersen.
1991.
AIDS related lymphoma. Histopathology, immunophenotype and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization.
Am. J. Pathol.
138:149-163[Abstract].
|
| 19.
|
Hardy, W. D.
1981.
Hematopoietic tumors of cats.
J. Am. Anim. Hosp. Assoc.
17:921-940.
|
| 20.
| Hentges, F. 1994. B lymphocyte ontogeny and
immunoglobulin production. Clin. Exp. Immunol.
97(Suppl.):3-9.
|
| 21.
|
Herndier, B. G.,
L. D. Kaplan, and M. S. McGrath.
1994.
Pathogenesis of AIDS lymphomas.
AIDS
8:1025-1049[Medline].
|
| 22.
|
Herndier, B. G.,
B. T. Shiramizu,
N. E. Jewett,
K. D. Aldape,
G. R. Reyes, and M. S. McGrath.
1992.
Acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation.
Blood
79:1768-1774[Abstract/Free Full Text].
|
| 23.
|
Hutson, C. A.,
B. A. Rideout, and N. C. Pedersen.
1991.
Neoplasia associated with feline immunodeficiency virus infection in cats of Southern California.
J. Am. Vet. Med. Assoc.
199:1357-1362[Medline].
|
| 24.
|
Ishida, T.,
T. Washizu,
K. Toriyabe,
S. Motoyoshi,
I. Tomodo, and N. C. Pedersen.
1989.
FIV infection in cats in Japan.
J. Am. Vet. Med. Assoc.
194:221-225[Medline].
|
| 25.
|
Jarrett, O.
1994.
Feline leukaemia virus, p. 473-487. In
E. A. Chandler, C. J. Gaskell, and R. M. Gaskell (ed.), Feline medicine and therapeutics.
Blackwell Scientific Publications Ltd., Oxford, United Kingdom.
|
| 26.
|
Kanavaros, P.,
P. Gaulard,
F. Charlotte,
N. Martin,
C. Ducos,
M. Lebezu, and D. Y. Mason.
1995.
Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas.
Am. J. Pathol.
146:735-741[Abstract].
|
| 27.
|
Kung, H.-J.,
C. Boerkoel, and T. H. Carter.
1991.
Retroviral mutagenesis of cellular oncogenes: a review with insights into the mechanisms of insertional activation.
Curr. Top. Microbiol. Immunol.
171:1-25[Medline].
|
| 28.
|
Laurence, J., and S. M. Astrin.
1991.
Human immunodeficiency virus induction of malignant transformation in human B lymphocytes.
Proc. Natl. Acad. Sci. USA
88:7635-7639[Abstract/Free Full Text].
|
| 29.
|
Lennert, K., and A. C. Feller.
1992.
.
Histopathology of non-Hodgkin's lymphomas: based on the updated Kiel classification.
Springer-Verlag, Berlin, Germany.
|
| 30.
|
Levine, A. M.
1992.
Acquired immunodeficiency syndrome-related lymphoma.
Blood
80:8-20[Free Full Text].
|
| 31.
|
Mason, D. Y.,
J. L. Cordell,
A. G. D. Tse,
J. J. M. Van Dongen,
C. J. M. Van Noesel,
K. Micklem,
K. A. Pulford,
F. Valensi,
W. M. Comans-Bitter,
J. Borst, and K. C. Gatter.
1991.
The IgM-associated protein mb-1 as a marker of normal and neoplastic B cells.
J. Immunol.
147:2474-2482.
|
| 32.
|
Mason, D. Y.,
C. J. M. Van Noesel,
J. L. Cordell,
W. M. Comans-Bitter,
K. Micklem,
A. G. D. Tse,
R. A. W. Van Lier, and J. J. M. Van Dongen.
1992.
The B29 and mb-1 polypeptides are differentially expressed during human B cell differentiation.
Eur. J. Immunol.
22:2753-2756[Medline].
|
| 33.
|
Miyazawa, T.,
T. Furuya,
S. Itagaki,
Y. Tohya,
E. Takahashi, and T. Mikami.
1989.
Establishment of a feline T-lymphoblastoid cell line highly sensitive for replication of feline immunodeficiency virus.
Arch. Virol.
108:131-135[Medline].
|
| 34.
|
Monroe, J. G., and L. E. Silberstein.
1995.
HIV-mediated B-lymphocyte activation and lymphomagenesis.
J. Clin. Immunol.
15:61-68[Medline].
|
| 35.
|
Neil, J. C.,
D. Hughes,
R. McFarlane,
N. M. Wilkie,
D. E. Onions,
G. Lees, and O. Jarrett.
1984.
Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias.
Nature
308:814-820[Medline].
|
| 36.
|
Nevins, J. R., and P. K. Vogt.
1996.
Cell transformation by viruses, p. 301-343. In
B. N. Fields, D. M. Knipe, P. M. Howley, R. M. Chanock, J. L. Melnick, T. P. Monath, B. Roizman, and S. E. Straus (ed.), Fields virology.
Lippincott-Raven, Philadelphia, Pa.
|
| 37.
|
Osborne, R.,
M. Rigby,
K. Siebelink,
J. Neil, and O. Jarrett.
1994.
Virus neutralisation reveals antigenic variation among feline immunodeficiency isolates.
J. Gen. Virol.
75:3641-3645[Abstract/Free Full Text].
|
| 38.
|
Penn, I.
1986.
The occurrence of malignant tumours in immunosuppressed states.
Prog. Allergy
37:259-300[Medline].
|
| 39.
|
Phillips, T. R.,
R. L. Talbott,
C. Lamont,
S. Muir,
K. Lovelace, and J. H. Elder.
1990.
Comparison of two host cell range variants of feline immunodeficiency virus.
J. Virol.
64:4605-4613[Abstract/Free Full Text].
|
| 40.
|
Poli, A.,
F. Abramo,
F. Baldinotti,
M. Pistello,
L. Da Prato, and M. Bendinelli.
1994.
Malignant lymphoma associated with experimentally induced feline immunodeficiency virus infection.
J. Comp. Pathol.
110:319-328[Medline].
|
| 41.
|
Ramsay, A. D.,
J. Giddings,
A. Baskerville, and M. P. Cranage.
1991.
Phenotypic analysis of malignant lymphoma in simian immunodeficiency virus infection using anti-human antibodies.
J. Pathol.
164:321-328[Medline].
|
| 42.
|
Rigby, M. A.,
E. C. Holmes,
M. Pistello,
A. Mackay,
A. J. Leigh Brown, and J. C. Neil.
1993.
Evolution of structural proteins of feline immunodeficiency virus: molecular epidemiology and evidence of selection for change.
J. Gen. Virol.
74:425-436[Abstract/Free Full Text].
|
| 43.
|
Rosenberg, M. P.,
A. E. Hohenhaus, and R. E. Matus.
1991.
Monoclonal gammopathy and lymphoma in a cat infected with feline immunodeficiency virus.
J. Am. Anim. Hosp. Assoc.
27:335-337.
|
| 44.
|
Sabine, M.,
J. Michelsen,
F. Thomas, and M. Zheng.
1988.
Feline AIDS.
Aust. Vet. Pract.
18:105-107.
|
| 45.
|
Shelton, G. H.,
C. K. Grant,
S. M. Cotter,
M. B. Gardner,
W. D. J. Hardy, and R. F. DiGiacomo.
1990.
Feline immunodeficiency virus and feline leukemia virus infections and their relationships to lymphoid malignancies in cats: a retrospective study (1968-1988).
J. Acquired Immune Defic. Syndr.
3:623-630.
|
| 46.
|
Shelton, G. H.,
M. L. Linenberger,
C. K. Grant, and J. L. Abkowitz.
1990.
Hematological manifestations of feline immunodeficiency virus infection.
Blood
76:1104-1109[Abstract/Free Full Text].
|
| 47.
|
Shelton, G. H.,
K. D. McKim,
P. L. Cooley,
P. F. Dice,
R. G. Russell, and C. K. Grant.
1989.
Feline leukemia virus and feline immunodeficiency virus infections in a cat with lymphoma.
J. Am. Vet. Med. Assoc.
194:249-252[Medline].
|
| 48.
|
Shiramizu, B.,
B. G. Herndier, and M. S. McGrath.
1994.
Identification of a common clonal human immunodeficiency virus integration site in human immunodeficiency virus-associated lymphomas.
Cancer Res.
54:2069-2072[Abstract/Free Full Text].
|
| 49.
|
Tarlington, D.
1994.
B-cell differentiation in the bone marrow and periphery.
Immunol. Rev.
137:203-229[Medline].
|
| 50.
|
Terry, A.,
J. J. Callanan,
R. Fulton,
O. Jarrett, and J. C. Neil.
1995.
Molecular analysis of tumours from feline immunodeficiency virus (FIV)-infected cats: an indirect role for FIV?
Int. J. Cancer
61:227-232[Medline].
|
| 51.
|
Verschuren, M. C. M.,
W. M. Comans-Bitter,
C. A. C. Kapteijn,
D. Y. Mason,
G. S. Brouns,
J. Borst,
H. G. Drexler, and J. J. M. Van Dongen.
1993.
Transcription and protein expression of mb-1 and B29 genes in human hematopoietic malignancies and cell lines.
Leukemia
7:1939-1947[Medline].
|
| 52.
|
Yamamoto, J. K.,
C. D. Ackley,
H. Zochlinski,
H. Louie,
E. Pembroke,
M. Torten,
H. Hansen,
R. Munn, and T. Okuda.
1991.
Development of IL-2-independent feline lymphoid cell lines chronically infected with feline immunodeficiency viruses: importance for diagnostic reagents and vaccines.
Intervirology
32:361-375[Medline].
|
J Virol, January 1998, p. 767-771, Vol. 72, No. 1
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Beatty, J., Terry, A., MacDonald, J., Gault, E., Cevario, S., O'Brien, S. J., Cameron, E., Neil, J. C.
(2002). Feline Immunodeficiency Virus Integration in B-Cell Lymphoma Identifies a Candidate Tumor Suppressor Gene on Human Chromosome 15q15. Cancer Res.
62: 7175-7180
[Abstract]
[Full Text]
-
Nesbit, C. E., Schwartz, S. A.
(2002). In Vitro and Animal Models of Human Immunodeficiency Virus Infection of the Central Nervous System. CVI
9: 515-524
[Full Text]
Top
Abstract
Text
