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Macrophage Tropism of Feline Leukemia Virus (FeLV) of Subgroup-C and
Increased Production of Tumor Necrosis Factor-a
by FeLV-Infected Macrophages
By Kanwar Nasir M. Khan, Gary J. Kociba, and Maxey L. Wellman
Erythroid aplasia is induced in cats by feline leukemia virus
(FeLV) of subgroup C but not by FeLV of subgroup A. In an
investigation of the role of macrophages in FeLV-C-induced
diseases, the concentrations of FeLV and tumor necrosis
factor-a (TNF-a) were compared between feline peritoneal
macrophagesincubated with FeLV of subgroupA or C. FeLV
of both subgroups infected macrophages, but expression
of FeLV-C was 21-fold higher than FeLV-A in peritoneal
macrophages (P = .004).
The supernatants of FeLV-Cinoculated macrophage cultures contained significantly
higher levels of TNF-a (70 +: 14 U/mL) at 72 hours postincubation compared with FeLV-A-inoculated (38 +: 8 U/
mL) and uninoculated(31 f 8 U/mL) cultures. Moreover,
a positive correlation was shown between cell-associated
FeLV surface glycoprotein gp70 and TNF-a expression in
FeLV-C-infected macrophages by immunofluorescence (r
= .6; P = .OOl), measured with a computer-assisted, laser-based digital imaging system. The addition of TNF-a to
a uniform population of FeLV-infected cells (feline embryonic fibroblasts) caused an enhancement of viral expression
(P < .05). These results indicate that FeLV-C has tropism
for macrophages, FeLV expression is positively correlated
with TNF-a expression in macrophages, and TNF-a enhances FeLV replication in fibroblasts. W e suggest that
FeLV-C infection of macrophages and secretion of TNF-cx
may be important in hematopoietic suppression in FeLVC-infected cats.
0 1993 by The American Society of Hematology.
F
In this study, the expression of FeLV and TNF-a were
compared in macrophages incubated with FeLV of subgroups
A and C. This report documents that both FeLV of subgroup
A and FeLV of subgroup C infect macrophages, but FeLV
expression in macrophages is 2 1-fold higher with FeLV-C
than with FeLV-A. The increased level of expression of FeLV
in FeLV-C-infected macrophages correlated with higher levels of TNF-a compared with FeLV-A-infected and uninfected
macrophages. It is suggested that FeLV-C is a monocytotropic
virus and that the enhanced expression of FeLV by FeLVC-infected macrophages is correlated with increased expression of TNF-a.
ELINE LEUKEMIA VIRUS (FeLV) is a retrovirus that
causes a wide range of proliferative and antiproliferative
diseases in cats, including leukemia, lymphoma, myelodysplasia, immunodeficiency syndrome, and erythroid aplasia.’
FeLV has three subgroups, A, B, and C, which reflect differences in the envelope protein gp70. The subgroups influence
infectivity, host range, and pathogenicity.I4 FeLV-A is primarily associated with neoplastic and immunodeficiency
diseases,’ whereas FeLV-C induces erythroid a p l a ~ i a .The
~,~
pathogenic mechanisms of FeLV-C-induced erythroid aplasia
are poorly understood. Although decreased numbers of bone
marrow (BM) fibroblasts have been reported in cats with
FeLV-C-induced erythroid aplasia,’ the role of macrophages
and other accessory cells of the BM microenvironment has
not been investigated.
Macrophages of the BM microenvironment play an important role in regulating hematopoiesis by synthesizing a
variety of stimulatory and inhibitory cytokines. Viral infections of macrophages may stimulate release of a variety of
cytokines such as prostaglandin E-2, interleukin-6 (IL-6), and
tumor necrosis factor-a (TNF-a).* Increased TNF-a production has been associated with retroviral infections, including human immunodeficiency virus (HIV) and simian
immunodeficiency virus (SIV)
The increased
TNF-a levels in HIV-infected patients correlate with the development of anemia and lymphopenia.“ SIV infection of
BM macrophages has been correlated with marked inhibition
of hematopoietic progenitors.’2 Recently, we showed cytotoxicity in cocultures of FeLV-C-infected fibroblasts and
normal feline BM-derived macrophages but not in cocultures
of FeLV-A-infected fibroblasts and macrophages. Supernatants of cocultures of FeLV-C-infected cells contained increased levels of TNF-a and the cytotoxicity was partially
inhibited by the addition of anti-TNF antibodiesL3Moreover,
cats infected with the anemogenic Kawakami-Theilen strain
of FeLV (FeLV-KT containing FeLV-C) have increased
serum levels of TNF-a.I4From these findingswe hypothesized
that FeLV-C has tropism for macrophages and stimulates
TNF-a production and that TNF-a is involved in the pathogenesis of FeLV-C-induced diseases.
Blood, Vol81, No 10 (May 15). 1993: pp 2585-2590
MATERIALS AND METHODS
Animals and sample collection. Six 8- to 10-week-old specific
pathogen-free (SPF) cats were used as sources of peritoneal macrophages. The cats were obtained from a breeding colony of SPF cats
maintained in the Department of Veterinary Pathobiology, The Ohio
State University. Cats were anesthetized with ketamine IM (25 mg/
kg) and xylazine HC1 IM (1 mg/kg) before intraperitoneal injection
and fluid collection.
Peritoneal macrophage collection and culture. Cats were injected
intraperitoneally (IP) with 100 mL of 3% thioglycollate(Difco Labs,
Detroit, MI) solution. After 48 hours, phosphate-buffered saline (PBS,
100 mL) was injected IP and was removed after 5 minutes with 18gauge catheters connected to 450-mL blood collection bag. Peritoneal
fluid mononuclear cells were separated by Percoll (1.071 g/mL;
Pharmacia, Fine Chemicals, Uppsala, Sweden) density-gradientcentrifugation as described previously for BM mononuclear cell separation with minor modifications.15 Briefly, peritoneal fluid samples
From the Department of Veterinary Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH.
Supported by National Institutes of Health Grant No. 41939.
Address reprint requests to Gary J. Kociba, DVM, PhD, Department
of Veterinary Pathobiology, The Ohio State University, I925 Coffey
Rd, Columbus, OH 43210.
The publication costs ofthis article were defrayed in part by page
charge payment. This article must therefore be hereby marked
“advertisement” in accordance with 18 V.S.C. section 1734 solely to
indicate this fact.
0 1993 by The American Society ofHematology.
0006-4971/93/8110-0038$3.00/0
2585
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2586
were centrifuged at 400g for 10 minutes at 4°C to concentrate the
cells. Concentrated cells were diluted with 10 mL minimal essential
medium-a (MEM-a; GIBCO Laboratories, Grand Island, NY)and
10 mL Hanks’ Balanced Salt Solution (HBSS; GIBCO) and underlayered with 10 mL Percoll (Pharmacia). Samples were centrifuged
at 400g for 20 minutes at 22°C. Interface cells were washed two times
in HBSS and resuspended at I X lo7 cells/mL in MEM-a.
To obtain adherent peritoneal mononuclear cells, 5 X IO6 cells/
mL were incubated for 72 hours at 37°C in 75-cm tissue-culture
flasks (Costar, Cambridge, MA) in 15-mL MEM-a containing 0.5%
bovine serum albumin (BSA; Intergen Co, Purchase, NY),glutamine
(2 mmol/L), 0.5%penicillin-streptomycin(GIBCO), 33% horse serum
(GIBCO), and 11%pokeweed-conditioned medium (PWCM) from
feline BM mononuclear cells. Nonadherent cells with medium were
removed from flasks after 24 and 48 hours and the cultures were
replenished with fresh medium. After 72 hours of incubation, adherent
cells were collected by scraping with a rubber policeman, washed
twice, and resuspended in MEM-a. Cells were stained with Giemsa
for morphologic evaluation and with a naphthyl butyrate esterase
(ANBE) for nonspecific esterase activity (Sigma, St Louis, MO). Positive staining for nonspecific esterase activity was detected in 8 1% +
8% of the cells.
Virus inoculation. FeLVs of subgroups A and C derived from
feline embryonic fibroblasts ( E A cells)2were kindly provided by Dr
Jennifer L. Rojko (The Ohio State University, Columbus). Viral inocula were standardized by virus infectivity assays.’ For in vitro FeLV
infection of peritoneal macrophages, 1 X IO7 cells were incubated
with biologically cloned FeLV-A or FeLV-C at a multiplicity of infection of 1 .O for 2 hours at 37°C. After 2 hours of incubation, cells
were washed twice with PBS to remove free virus before culturing in
12-well plates.
TNF-a and FeLV determinations. Peritoneal macrophages were
cultured at 1 X IO6 cells per well in 1.5-mL media in 12-well tissue
culture plates (Costar) at 37°C in a humidified atmosphere containing
5% C 0 2 and 10%02.Culture supernatants (1 10 pL) were collected
after 2,24, 72, and 168 hours postincubation for TNF-a and FeLV
p27 determinations. Culture supernatants were centrifuged at 560g
for 10 minutes at 4°C to remove cellular elements and stored at
-70°C.
TNF-a was measured using a bioassay involving the TNF-sensitive
L-929 cell line16and the MTT tetrazolium assay as described below.
A standard curve was made using recombinant human TNF-a (Genzyme C o p , Cambridge, MA). The 27,000-dalton core protein (p27)
of FeLV was detected in cells on cytocentrifuged slides by use of an
indirect immunofluorescent assayI7 and in culture supernatants by
a modified enzyme-linked immunosorbent assay (ELISA) (FeLV antigen test kit; Synbiotics Co, San Diego, CA).
Quantitative analysis of cell-associatedFeLV and TNF-a in peritoneal macrophages. In selected experiments, peritoneal macrophages were collected from 12-well plates 72 hours after FeLV inoculation. Cells were dually stained for FeLV antigen and TNF-a.
Briefly, cytocentrifuge preparations fixed in cold methanol were incubated with 1:20 dilution of mouse monoclonal anti-FeLV gp70
antibodies (kindly provided by Dr Jennifer L. Rojko) and 1:40 dilution
of polyclonal rabbit anti-TNF antibodies (Genzyme) simultaneously
for 1 hour at 37°C in a humidified atmosphere. After incubation,
slides were washed twice in PBS for 5 minutes each, and rinsed in
distilled water. Slides were then incubated with 130 dilution of phycoerythrocin (PE)-labeled goat anti-mouse IgG antibodies and 1 :80
dilution of fluorescein isothiocyanate (HTC)-labeled goat anti-rabbit
IgG antibodies (Southern Biotech Assoc, Birmingham, AL) simultaneously for 1 hour at 37°C in a humidified atmosphere. After the
second incubation, slides were washed twice in PBS for 5 minutes
each, rinsed with distilled water, and mounted with 50% glycerine
KHAN, KOCIBA, AND WELLMAN
in PBS. Slides incubated with mouse anti-FeLV alone, polyclonal
rabbit anti-TNF alone, PE-labeled anti-mouse IgG alone, and FITClabeled anti-rabbit IgG alone were used as controls.
The ACAS 570 interactive laser cytometer (Meridian Instruments,
Okemos, MI) is a computer-assisted, laser-based digital imaging system for quantitative and distributional analysis of fluorescencesignals
of anchoragedependent cells. An inverted phasecontrast microscope
with a microprocessor-controlled stage is used to rapidly transport
cells past the microscope objective. At preselected intervals, a laser
beam is pulsed and the resultant fluorescent emission is detected with
a sensitive photomultiplier tube. The collected data are displayed on
a color monitor as a fluorescent intensity curve of a cross-sectional
profile or as a pseudocolor, two-dimensional image of a scanned area.
FeLV-infected and control cells were analyzed with the ACAS 570
interactive laser cytometer” with an argon laser tuned to 488-nmexciting wavelength and three optical filters: 555 DRLP, 530/30 BP,
and 575 DF25 for PE and FITC. Cells were randomly selected and
at least 40 cells per experiment were analyzed from each culture of
FeLV-A-infected, FeLV-C-infected, and uninfected macrophages in
four independent experiments. The average integrated fluorescence
for PE and FITC for each cell was computed. The background fluorescence observed in control cells treated with PE- and FITC-labeled
antibodies only was subtracted from the fluorescence observed in
FeLV-A-infected, FeLV-C-infected, and uninfected cells treated with
anti-gp70/anti-TNF-a antibodies and PE-labeled/FITC-labeled antibodies.
TNF-a treatment of FeL V-inficted fibroblasts. FeLV-infected
FEA cells were kindly provided by Dr Jennifer L. Rojko? To study
the effect of TNF-a on FeLV expression, 1 X 1O6 FeLV-A-infected
fibroblastsor FeLV-C-infected fibroblasts were incubated with 0, 10,
100, or 1,000 U/mL of recombinant human TNF-a (Genzyme) in
200 p L media at 37°C for 2 hours in humidified atmosphere and
cultured in 6-well tissue-culture plates in 2 mL media containing
84%Dulbecco’s MEM (GIBCO), 15%heat-inactivatedfetal calf serum
(FCS) (Hazelton Res Products, Lenexa, KS), and 1% penicillin-streptomycin at 37°C in a humidified atmosphere containing 5% C 0 2
and 10%0 2Culture
.
supernatants were collected after 48 hours for
assay of FeLV p27.
Colorimetric MTT tetrazolium assay. In selected experiments,
the MTT tetrazolium assay was performed as described’’ with modifications to measure viability of peritoneal macrophages and FEA
cells. In brief, 1 X lo4 cells in 100 pL media were cultured in 96well tissue culture plates (Costar) for 2, 24, 72, or 168 hours. After
specific incubation periods, 20 pL of MTT solution (5 mg/mL) were
added to each well and plates were incubated for 4 hours at 37°C
for cleavage of MTT. After the incubation, 100 pL extraction buffer
containing 20% sodium dodecyl sulfate (SDS) and 50%N.N-dimethyl
fonnamide (Sigma) were added to each well and plates were incubated
overnight at 37°C. Absorbance was measured using an ELISA plate
reader (Molecular Devices, UV Max) with a test wavelength of 580
nm and a reference wavelength of 650 nm.
Endotoxin screening. FEA cells and media were screened for endotoxin and were found to be negative at the 0.015 endotoxin unit
(EU) level by the Limulus amoebocyte lysate assay (E-Toxate; Sigma).
Statistical analysis. Data were analyzed using one-way analysis
of variance at 95% level of significance and simple linear regression
and correlation. Multiple comparisons were made using the Bonferroni method of multiple comparisons.
RESULTS
Diferential expression of F e L V by macrophages infected
with FeLV-A versus FeLV-C. FeLV infection of macrophages was documented by increased p27 levels in the supernatants of cultures inoculated with FeLV. Both FeLV-A
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MACROPHAGE TROPISM OF FELV OF SUBGROUP C
terval. No media changes were performed after inoculation
of cultures. The MTT colorimetric assay documented similar
cell growth patterns in FeLV-A-inoculated, FeLV-C-inoculated, and control cultures. By indirect immunofluorescent
assay for FeLV p27 viral core protein, the proportion of
FeLV-infected macrophages was only slightly higher in cultures inoculated with FeLV-C compared with those inoculated with FeLV-A. Viral antigen was detected in 52% ? 5%
of cells of cultures inoculated with FeLV-A and in 78% f
9% of cells of cultures inoculated with FeLV-C. The mean
number of cells expressing p27 in cultures inoculated with
FeLV-C (78% -+ 9%) was similar to the mean percentage of
cells that were positive for butyrate esterase (81% k 8%) at
the time of initiation of cultures.
x
A
m
d
3
a!
0
r0
.d
\
Correlation of TNF-a with FeLV p27 levels in FeLV-inoculated macrophages. TNF-a was detected in the supernatants of all cultures of macrophages after 2 hours of incubation. The TNF-a levels in all cultures were increased
slightly after 24 hours incubation but no significantdifferences
were detected among FeLV-inoculated and control cultures.
Whereas TNF-a levels declined after 24 hours in FeLV-Ainoculated and control cultures, TNF-a increased in the supernatants of FeLV-C-inoculated macrophage cultures to
peak levels of 70 ? 14 pg/mL (P = .058) at 72 hours postincubation (Fig 2). The increase in TNF-a levels in FeLV-Cinoculated macrophage cultures correlated with the increased
FeLV p27 levels in the same cultures 72 hours postincubation.
Correlation of expression of FeL V and TNF-a in individual
infected macrophages. To correlate the expression of FeLV
Time (hours)
n
2
w
t
1
1.6
90
-1
0.6
I
I
I
*
I
I
I
I
T
80
-
70
0.4
0
I
1
I
I
I
I
I
24
48
72
96
120
144
168
60
Time (hours)
50
Fig 1. FeLV p27 levels in supernatants of FeLV-A- and FeLVC-inoculated macrophage cultures and cell viability. Peritoneal
macrophages were collected from normal SPF cats and were inoculated with FeLV-A or FeLV-C as described in Materials and
Methods. The 27,000-dalton core protein (p27) of FeLV was measured using a modification of a commercially available ELSA kit
(Synbiotics Co). The cell viability was evaluated using colorimetric
M l T assay as described in Materials and Methods. Results represent
mean f SEM from six independent experiments. *P < .05 significantly different from FeLV-A. (0)FeLV-A, (V)FeLV-C; (0) control.
40
30
20
10
t
0'
o
and FeLV-C infected macrophages, but expression of FeLVC was 21-fold higher than FeLV-A in these cells. As shown
in Fig 1, significantly higher levels of FeLV p27 were present
in the supernatants of macrophage cultures inoculated with
FeLV-C compared with FeLV-A at 72 hours ( P = .004)and
168 hours ( P = .007) postinoculation. The FeLV p27 levels
peaked at 39.2 S 9.58 ng/107 cells in FeLV-C-infected cultures at 72 hours postinoculation compared with 1.9 l 0.82
&lo7 cells in FeLV-A-inoculated cultures at the same in-
j
I
I
24
48
I
I
I
72
96
120
I
I
144 1 6 8
Time (hours)
Fig 2. TNF-a levels in culture supernatants of macrophage cultures inoculated with FeLV-A or FeLV-C and uninoculated controls.
Peritoneal macrophageswere collected from normal SPF cats and
were inoculated with FeLV-A or FeLV-C as described in Materials
and Methods. TNF-a titers were measured in culture supernatants
by a bioassay using the TNF-sensitive L929 cell line as described
in Material and Methods. Results represent mean 2 SEM TNF U/
mL from six independent experiments. *P = .058 significantly different from FeLV-A and control. (V) FeLV-A; (V)FeLV-C; (0)control.
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2588
KHAN, KOCIBA, AND WELLMAN
3.5
3.0
,
1
I
I
I
*
T
FELV-A
c
I
I
FELV-C
I
CONTROL
I
I
t
0’3
I
rescence per cell attributed to FeLV gp70 was significantly
higher (P= .02) in FeLV-C-inoculated cells compared with
FeLV-A-inoculated cells (Fig 3). Similarly, average integrated
fluorescenceper cell related to TNF-a was significantly higher
in FeLV-C-inoculated cells compared with FeLV-A-inoculated (P= .04) and uninoculated cells (P= .014). Although
the average integrated fluorescence per cell for cell-associated
TNF-a was higher in FeLV-A-inoculated cells compared with
uninoculated cells, the difference was not statistically significant (Fig 3). There was a significant and positive correlation
between FeLV expression and TNF-a expression in FeLVC-inoculated macrophages (r = .6;P = .001). When the
FeLV-negative cells were excluded from the analysis, the
correlation between FeLV expression and TNF-a expression
was stronger (r = .8;P = .001).
Effects of TNF-a on expression of FeL V in infectedjibroblasts. The immunofluorescent studies of coexpression of
FeLV and TNF-a showed a correlation between TNF
expression and FeLV protein concentration in macrophages.
It was not clear whether TNF-a enhanced FeLV expression.
This issue was addressed in fibroblasts by characterization of
FeLV expression in FEA cells that were uniformly infected
with FeLV-A or FeLV-C. The addition of TNF-a (1,000 U/
mL) to FeLV-infected fibroblasts (FEA cells) caused a significant enhancement of viral expression as indicated by increased levels of p27 antigen in culture supernatants (P <
.05). Similar enhancement was detected in fibroblasts infected
with FeLV-A versus those infected with FeLV-C (Fig 4). No
250
*
I
T
200
h
0.0
FELV-A
FELV-C
CONTROL
2
-9
v
Fig 3. Cell-associatedTNF-a expression and FeLV expression in
peritoneal macrophages from cultures inoculated with FeLV-A,
FeLV-C, and uninoculated controls. Seventy-two hours postincubation, the macrophages were dually stained for FeLV gp70 and
TNF-a as described in Materials and Methods. Cells were analyzed
using an ACAS 570 interactive laser cytometer (Meridian Inc, Okemos. MI). Results represent mean ? SEM-integratedfluorescence
per cell (10’) from four independentexperiments. ‘P < .05 significantly different from FeLV-A and control.
with the expression of TNF-a on an individual cell basis,
immunofluorescent studies were performed on cultured
macrophages after dual labeling with antibodies to FeLV gp70
and TNF-a. Cells of macrophage cultures inoculated with
FeLV-A or FeLV-C and uninoculated control cells were
treated with primary murine anti-FeLV gp70 antibodies and
rabbit anti-TNF-a antibodies and stained with secondary
antibodies labeled with PE (anti-gp70) or FITC (anti-TNF-a).
Individual cells were analyzed for relative fluorescent intensity
and distribution of both labels with a computer-assisted, laserbased digital imaging system. The average integrated fluo-
&
a
150
3
L
I
-
U
1000
TNF Concentr at.ion (units/i
Fig 4. Enhancement of FeLV expression in FeLV-infected FEA
cells by TNF-a. FeLV-A-infected or FeLV-C-infected FEA cells were
cultured in the presence of 1,000 U/mL rhTNF-a in 12-well plates
and in 96-well plates for 48 hours at 37°C in a humidified atmosphere. Culture supernatants were collected from 12-well plates
after 48 hours and FeLV p27 was measured using a modification
of a commercially available ELISA kit (Synbiotics Co). Results represent mean 2 SEM from four independentexperiments. *P < .05
significantly different from control. (m) FeLV-A; (0)FeLV-C.
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MACROPHAGE TROPISM OF FELV OF SUBGROUP C
significant effect on growth of fibroblasts was observed with
these concentrations of TNF-a. A similar dose-dependent
enhancement of virus replication was observed with 10 and
100 U/mL of TNF-a in FeLV-infected fibroblasts (data not
shown).
DISCUSSION
2589
shown to potentiate TNF effects.35FeLV-C-infected erythroid
cells may acquire enhanced susceptibility to the inhibitory
effects of TNF-a through an increased palmitate production.
Macrophage dysfunctions, including defects in monocyte to
macrophage maturation, have been reported in human retroviral infection^.^^ Similar functional abnormalities in FeLVinfected macrophages, in addition to increased TNF-a production, may impair erythroid progenitor and macrophage
interactions. A defect in monocyte maturation has been suggested to play a role in the pathogenesis of aplastic anemia
in humans.37
In this study, we showed that both FeLV of subgroup A
and FeLV of subgroup C infect macrophages, but FeLV
expression in macrophages is 2 1-fold higher with FeLV-C
than with FeLV-A. The high level of expression of FeLV in
FeLV-C-infected macrophages correlates with higher levels
of TNF-a compared with FeLV-A-infected macrophages. It
is suggested that FeLV-C is a monocytotropic virus and that
increased expression of TNF-a by FeLV-C-infected macrophages may play a role in the pathogenesis of erythroid
aplasia in FeLV-infected cats.
In this study we showed that macrophages are target cells
for FeLV of subgroup C. FeLV-C was expressed at 2 1-fold
higher levels in peritoneal macrophages compared with FeLVA. The finding that FeLV-A was expressed only at low levels
in peritoneal macrophages is in agreement with previous
studies of Hoover et a120 with the Rickard strain of FeLV
(FeLV-R) that contains subgroups A and B. In their experiments with FeLV-R, treatment with hydrocortisone was required to make macrophages permissive to FeLV-R infection.
In contrast, in these studies, infection of untreated peritoneal
macrophages in vitro with FeLV-C resulted in high levels of
virus expression. Recently, we showed that macrophages from
the BM also are susceptible to infection with FeLV-C in vitro. l 3 Persistent infection of BM macrophages is associated
with other retroviral infections including HIV- 1 and
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SIV.12,21,22
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roviruses, in Sherding RG (ed): The Cat, Diseases and Clinical Manoccurs in soluble and cell-associated forms.23The cell-assoagement, vol 1. New York, NY, Churchill Livingstone, 1989, p 229
ciated form of TNF-a kills tumor cells and virus-infected
2. Jarrett 0, Laird HM, Hay D Determinants of the host range
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of feline leukaemia viruses. J Gen Virol 20: 169, 1973
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~
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replicati~n.~*,~~
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65:280, 1991
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ony-forming units-granulocytes/monocytes (CFU-GM) are
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~ n a f f e c t e d . ~We
~ . ~recently
’
have shown that feline erythroid
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topoietic progenitor cell growth. J Virol 64:656, 1990
of T N F a 3 ’ The erythroid progenitors have been shown to
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be infected with FeLV-C in experimentally induced feline
in feline leukemia virus subgroup-C infected fibroblasts is mediated
erythroid aplasia.33FeLV-C-infected thymic lymphoma cells
by adherent bone marrow mononuclear cells. In Vitro Cell Dev Bio
exhibit increased palmitic acid proportion^,^^ which has been
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49:231, 1988
16. Aggarwal BB, Kohr WJ, Hass PE, Moffat B, Spencer SA, Henzel WJ, Bringman TS, Nedwin GE, Harkins RN: Human tumor
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From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
1993 81: 2585-2590
Macrophage tropism of feline leukemia virus (FeLV) of subgroup-C
and increased production of tumor necrosis factor-alpha by
FeLV-infected macrophages
KN Khan, GJ Kociba and ML Wellman
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