![[Feedback]](/icons/banner/feedbackACT.gif)
![[For Subscribers]](/icons/banner/subscriberACT.gif)
![[Archive]](/icons/banner/archiveACT.gif)
![[Search]](/icons/banner/searchACT.gif)
![[Contents]](/icons/banner/tocACT.gif)
Previous Article | Next Article 
J Virol, June 1998, p. 5239-5244, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Rabbit Genital Tissue Is Susceptible to Infection
by Rabbit Oral Papillomavirus: an Animal Model for a Genital
Tissue-Targeting Papillomavirus
Stephen B.
Harvey,1
Nancy M.
Cladel,2
Lynn R.
Budgeon,2
Patricia A.
Welsh,2
James W.
Griffith,1
C. Max
Lang,1 and
Neil D.
Christensen2,3,*
Department of Comparative
Medicine,1
The Jake Gittlen Cancer
Research Institute,2 and
Department of
Microbiology and Immunology,3 The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033
Received 13 November 1997/Accepted 6 March 1998
 |
ABSTRACT |
Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus
which naturally infects oral mucosal sites of domestic rabbits. In this
study, we tested the hypothesis that rabbit genital mucosa is also
susceptible to ROPV infection by using the athymic mouse xenograft
system and adult immunocompetent rabbits. Subrenal xenografts of
ROPV-infected rabbit vulvar and penile sheath tissues were strongly
positive for ROPV infection by histologic, in situ hybridization, and
Southern analyses. Direct inoculation of adult rabbit penises with
infectious ROPV produced small raised lesions of approximately 1 by 1 by 1 mm that were ROPV positive by both in situ hybridization and
Southern analyses and were also viral capsid antigen positive by
immunohistological staining. Infection of rabbit genital tissues with
ROPV may be a useful animal model for the study of genital
tissue-targeting papillomaviruses.
| |
TEXT |
Rabbit oral papillomavirus (ROPV) is
a mucosatropic papillomavirus (PV) that causes tongue and oral
cavity papillomas in domestic rabbits (8, 17, 20, 21, 25,
26). ROPV does not infect cutaneous sites, is antigenically
unrelated to cottontail rabbit PV (CRPV), and induces papillomas which
spontaneously regress (7, 17, 21). One additional contrast
between ROPV- and CRPV-induced lesions of domestic rabbits is that
papillomas induced by ROPV are virion rich (17) whereas
those induced by CRPV are virion poor (23).
Currently, there are no laboratory animal model systems available for
study of experimental infection and transmission of genital
tissue-targeting PVs in intact hosts. Recent reports have described the
detection and characterization of genital PVs in several primate
species (3, 11, 15, 16, 19). However, isolation of
infectious virions and experimental infection and transmission were not
reported. It would thus be advantageous to develop a genital
tissue-targeting mucosal PV animal model system in a small laboratory
animal. A potential candidate for a genital tissue-targeting PV is
ROPV, which is a spontaneous infection of domestic rabbits (17,
25, 26). ROPV, when combined with CRPV, may offer a unique animal
model system for study of aspects of PV tissue specificity and host
immunity and provide a close approximation to the human disease in
which patients are susceptible to infection by mucosal and cutaneous
tissue-targeting human PV (HPV) types.
Mucosatropic animal PV systems that are currently available for study
include bovine PV type 4 infection of cattle and canine oral PV
infection of dogs. Both of these mucosal tissue-targeting PVs are
confined to oral mucosal tissues, the alimentary tract, and external
lips of the mouth (2, 6, 18). The two models have been used
to study some key events in PV infection of mucosal surfaces and host
immune responses to PV infection (1, 4, 10, 24). A third PV
mucosatropic model, involving an oral PV of hamsters, has been
described recently (9). However, successful infection of
genital mucosal tissues in these models has not been reported.
Our laboratory has recently produced high-titer stocks of infectious
ROPV with the athymic mouse xenograft system (5). The seed
stock of infectious ROPV was obtained from papillomas found on the
undersurfaces of the tongues of several domestic New Zealand White
rabbits. PCR amplification techniques indirectly detected ROPV DNA with
primers designed from previously published partial ROPV sequence data
(14). We have sequenced the entire genome of a cloned
isolate of this virus, and the data confirm that the virus is ROPV
(data not shown).
The objective of this study was to determine whether rabbit genital
tissues were susceptible to ROPV infection. Infectivity studies were
conducted in both immunodeficient (xenografted athymic mouse) and
immunocompetent (adult male rabbit) environments. Previous attempts to
directly infect rabbit genital tissues with ROPV were unsuccessful,
leading to the conclusion that the virus infects only oral mucosal
tissue (17, 25). However, some preliminary studies in our
laboratory have suggested that ROPV may infect rabbit genital tissues
when grafted under the renal capsules of athymic nude mice
(5).
ROPV infection in xenografts of adult and newborn rabbit
tissues.
Adult and newborn rabbits were initially used to analyze
the tissue susceptibility of ROPV infection in an immunodeficient environment. Fragments of mucosal epithelial tissues from the tongue,
penis, cervix, vagina, and larynx were incubated for 1 h in a 1:5
dilution of ROPV suspension at 37°C and surgically implanted beneath
the renal capsules of athymic mice, as previously described (5,
13). For each source of mucosal tissue, between 8 and 16 xenografts (2 per mouse) were attempted. Grafts were harvested 60 days
later for histological analysis, in situ hybridization, and Southern
analysis. For Southern analysis, genomic DNA was digested with the
SpeI restriction enzyme, which linearizes ROPV DNA, and
electrophoresed on 2% agarose gels. DNA was detected with a
32P-labeled full-length ROPV genomic probe cloned into a
modified pUC19 plasmid at the SpeI restriction site,
according to the manufacturer's instructions (New England Biolabs,
Beverly, Mass.). In situ hybridization assays used a subgenomic
fragment of ROPV (a 3.8-kb EcoRV fragment) that was cloned
into plasmid pcDNA3 (Invitrogen, Carlsbad, Calif.). The 3.8-kb viral
insert was purified from the plasmid, biotinylated (Amersham, Arlington
Heights, Ill.), and used as an in situ probe for the detection of ROPV
DNA. Control probes were HPV-11 and CRPV DNA, and control tissues were
HPV-11-infected human tissues and CRPV-infected rabbit tissues.
Xenografts from some of the mucosal sites were pooled for Southern
analysis. The results of these experiments are summarized in Table 1.
Histologically, xenografts derived from tongue tissue contained areas
of acanthosis and vacuolation of squamous epithelial cells, with in
situ hybridization-positive nuclei (5). In general, subrenal
xenografts derived from adult rabbit tissues were considerably smaller
than xenografts derived from newborn rabbit tissues. These observations
are in agreement with our earlier studies, in which newborn tissues
produced substantially larger xenografts than adult tissues when human
tissues were infected with HPV-11 (12) or when rabbit
tissues were infected with CRPV (unpublished observations). Subrenal
xenografts derived from other adult mucosal tissues contained only a
few areas of mild acanthosis and vacuolation of squamous epithelial
cells and no in situ hybridization-positive nuclei (data not shown).
Strong in situ hybridization signals, however, were obtained for 1 of
10 adult vaginal and 1 of 4 adult penile subcutaneous xenografts (Table
1), showing that adult genital tissues
were susceptible to ROPV infection. Southern analysis of pooled
xenografts from the adult mucosal tissues demonstrated strong signals
for ROPV DNA from tongue and penile tissues and weak signals from the
other mucosal tissues (Fig. 1; Table 1).
View this table:
[in this window]
[in a new window]
|
TABLE 1.
Tissue susceptibilities of adult and newborn rabbit
tissues to ROPV infection with the xenograft systema
|
|
View larger version (48K):
[in this window]
[in a new window]
|
FIG. 1.
Southern blot analysis of ROPV DNA in adult penile or
kit penile sheath xenografts in athymic mice. DNA was extracted from
the xenografts, digested with SpeI, and loaded into wells of
an agarose gel. After transfer of DNA to nylon membranes, the membranes
were probed with a 32P-labeled ROPV DNA probe.
Densitometric scanning of lanes was used to calculate the quantity of
ROPV DNA with three standards (lanes A [100 pg], B [1,000 pg], and
C [10,000 pg], insert ROPV DNA). Concentrations of ROPV DNA
(picograms of ROPV DNA per microgram of total genomic DNA) for each
sample were as follows: lane 41 (kit tongue xenograft), 12,500 pg; lane
42 (adult penis, uninfected), <10 pg; lanes 6, 18, and 3 (adult rabbit
penile xenografts), 150, 600, and <10 pg, respectively; lanes 32, 34, 36, and 33 (kit rabbit penile xenografts), 12,500, 10,500, 12,500, and
40 pg, respectively. Lane Kb, markers.
|
|
Newborn rabbit tissues were also tested for tissue susceptibility to
ROPV infection. Four to eight xenografts (two per mouse) for each
mucosal tissue type were attempted (Table 1). Xenografts from tongue
(5), vulvar (Fig. 2A), and
penile sheath (Fig. 2C) tissues contained marked hyperplasia and
acanthosis of the squamous epithelial cells. Some vacuolated epithelial
cells with clear cytoplasms, and epithelial cells with intranuclear
inclusions, were present in the stratum spinosum. Numerous darkly
stained in situ hybridization-positive nuclei were present in
xenografts of the ROPV-infected newborn vulva (Fig. 2B) and penile
sheath (Fig. 2D). Xenografts from vaginal tissues contained little or no histological changes (Fig. 2E) and no in situ hybridization-positive nuclei (data not shown). Southern analysis of individual newborn tissue
xenografts yielded strong positive signals for tissues from the tongue,
external penile sheath (Fig. 1), and vulva (Fig. 3) but only weak positive signals from
vaginal tissues (data not shown).
View larger version (109K):
[in this window]
[in a new window]
|
FIG. 2.
Histological and in situ hybridization analyses of
ROPV-infected rabbit kit xenografts of vulva (A and B), penile sheath
(C and D), and vagina (E). Hematoxylin and eosin staining of tissue
sections is shown in panels A, C, and E; in situ hybridization with a
subgenomic ROPV DNA probe of serial tissue sections is shown in panels
B and D. Magnification, ×100.
|
|
View larger version (41K):
[in this window]
[in a new window]
|
FIG. 3.
Southern blot analysis of ROPV DNA in kit vulvar
xenografts in athymic mice. DNA was prepared as described in the legend
to Fig. 1. After transfer of DNA to nylon membranes, the membranes were
probed with a 32P-labeled ROPV DNA probe. Concentrations of
ROPV DNA (picograms of ROPV DNA per microgram of total genomic DNA)
were calculated as described in the legend to Fig. 1 and were as
follows: lane 41 (kit tongue xenograft), 12,500 pg; lane 43 (adult
vulva, uninfected), <10 pg; lanes 26 to 31 (kit vulva xenografts),
1,250, 34,000, 40, 670, 40, and 18,000 pg, respectively. Lanes A (100 pg), B (1,000 pg), and C (10,000 pg), insert ROPV DNA; lane Kb,
markers.
|
|
Detection of genital ROPV infection in adult (immunocompetent)
rabbits.
New Zealand White adult male rabbits were used to
determine whether genital tissues in intact hosts supported ROPV
infection. Seventeen rabbits (in a total of four experiments) were
anesthetized, and the dorsal mucosal penile surfaces were superficially
wounded by 10 to 20 needle punctures/penis with a 25-gauge needle held at a shallow angle to the mucosal surfaces. An undiluted virus suspension was placed onto the wounded areas, and the animals were
allowed to recover from anesthesia. Animals were euthanized at 6 to 8 weeks postinfection, and penile tissues were harvested for histology,
in situ hybridization, and Southern analysis. In one set of
experiments, six male rabbits were infected with ROPV, of which three
rabbits were treated with a regime of cyclosporine A (CsA)
(22) to induce specific immune suppression. The dosing regime of CsA consisted of twice weekly subcutaneous injections of CsA
(Sandoz Pharma Ltd., Basel, Switzerland) to achieve a dose of 20 mg/kg
of body weight for 50 days, beginning on the day of ROPV infection.
After direct penile inoculation with ROPV, rabbits were examined at 28, 35, and 42 days postinfection for evidence of papilloma development.
Small raised lesions measuring 1 by 1 by 1 mm were noted grossly by 28 to 35 days postinfection on 10 of 17 rabbits (see Fig.
5). These lesions quickly regressed by 50 to 60 days. Nine of the 17 infected rabbits were euthanized at 42 days
(one at 56 days) postinfection, and penile tissues were harvested for histological analysis, in situ hybridization, and Southern analysis. The remaining eight rabbits were inspected weekly until the lesions had
completely regressed, at 60 days postinfection. Of the nine infected
rabbits from which tissues were harvested, several showed some
histological evidence of viral infection (Fig.
4). These characteristics included
acanthosis and hyperplasia of the squamous epithelium, strong in situ
hybridization signals for ROPV DNA, and PV
group-specific-antigen-positive nuclei, as revealed by immunohistological staining (Fig. 4). Penile DNA extracted from five of
eight infected rabbits (including two rabbits with raised lesions) were
strongly positive for ROPV DNA by Southern analysis (see Fig.
6).
View larger version (149K):
[in this window]
[in a new window]
|
FIG. 4.
Histologic, in situ hybridization, and capsid antigen
immunostaining analyses at 56 days postinfection of adult rabbit penile
epithelium of a CsA-treated rabbit infected with ROPV. (A, B, and C)
Five-micrometer sections through penile papillomas. (D) Uninfected
penile skin. Panels A and D show hematoxylin and eosin staining, panel
B shows in situ hybridization with an ROPV DNA probe, and panel C shows
capsid antigen immunohistological staining with the PV group-specific
antigen antibody. Magnification, ×90.
|
|
View larger version (50K):
[in this window]
[in a new window]
|
FIG. 5.
ROPV-challenged ventral lingual (magnification, ×1.66)
(A) and dorsal penile (magnification, ×0.83) (B, C, and D) surfaces.
Small discrete papillomas are easily observed on the underside of the
tongue. Several small raised papillomas are seen on the dorsal surface
of the penis. Rabbit G0850 (no CsA treatment) at day 30 (B) and day 56 (C) and rabbit G0856 (CsA treated) at day 56 (D) are shown. Note the
regression of penile papillomas by day 56 for rabbit G0850.
Confirmation that these lesions contained ROPV was conducted by in situ
hybridization with ROPV DNA probes (Fig. 4).
|
|
View larger version (42K):
[in this window]
[in a new window]
|
FIG. 6.
Southern blot analysis of ROPV DNA in penile tissues of
adult rabbits that were directly challenged with ROPV. Concentrations
of ROPV DNA (picograms of ROPV DNA per microgram of total genomic DNA)
were calculated as described in the legend to Fig. 1 and were as
follows: lane 4 (adult tongue xenograft), 190 pg; lane 42 (adult penis,
uninfected), <10 pg; lanes 16 to 40 (adult penile DNA from infected
rabbits), 300, 250, <10, <10, <10, 20, 35, and 20 pg, respectively.
Lanes A (100 pg), B (1,000 pg), and C (10,000 pg), insert ROPV DNA;
lane Kb, markers.
|
|
Histological evidence of lymphocytic infiltration was also visible at
42 days postinfection in most of the penile sites (data not shown),
suggesting an immune response possibly leading to regression.
Consistent with these findings was the observation that these raised
penile lesions regressed by 60 days (Fig. 5). While ROPV DNA was not
detected in sites with lymphocytic infiltrates by in situ
hybridization, Southern analysis revealed strong positive ROPV signals
from penile DNA in five of eight inoculated rabbits. We also noted that
ROPV lesions of the tongue that contained lymphocytic infiltrate were
in situ hybridization negative, as observed for penile lesions with
lymphocytic infiltrate (data not shown). These data suggest that the
lymphocytes infiltrating regressing lesions may have an early effect
upon the papillomas by reducing the levels of ROPV DNA detected by in
situ hybridization. Also consistent with these findings was the
observation of a strong in situ ROPV DNA signal and an absence of
lymphocytic infiltrates in penile lesions of a rabbit treated with CsA
(Fig. 5). We observed that ROPV-induced lesions of the tongues and
penises of rabbits treated with CsA persisted longer than those of
nonimmunosuppressed rabbits (Fig. 5).
Infectious ROPV is produced in ROPV-infected xenografted kit
genital tissues.
Juvenile and young adult rabbits (three females
and three males) were used to determine whether infectious ROPV virions
had been successfully passaged through xenografted kit genital tissues. Small raised lesions measuring 2 by 2 by 1 mm were noted grossly on the
ventral lingual surfaces of all six rabbits by 28 days postinfection
(Fig. 5). Additionally, small raised lesions measuring 2 by 2 by 1 mm
were noted on the dorsal penile surface of one male, and lesions
measuring 1 by 1 by 1 mm were noted on a second rabbit (data not
shown). A third rabbit showed no penile lesions. These experiments
demonstrated that kit penile sheath tissues and kit vulvar tissues can
support the full replication cycle of ROPV when the infected tissues
are xenografted into athymic mice. This system may provide a method for
developing a genital tissue-targeting variant of ROPV or a stock of
ROPV with an increased titer of infectivity for genital tissues (our
current stock of ROPV was prepared from tongue tissue xenografts).
Previous attempts to infect genital tissues with ROPV had been
unsuccessful, leading investigators to conclude that the virus infects
only oral tissues (17, 25). However, it is possible that the
concentration of ROPV used for infection was insufficient for
successful infection of genital mucosa. In these earlier studies, the
challenged genital sites were grossly inspected only for signs of PV
infection. In our studies, we used the athymic mouse xenograft system,
which allowed us to infect fragments of oral and genital tissues with
ROPV in an immunodeficient environment and thus produce high titers of
infectious virions. We observed that genital mucosal tissues of intact
hosts appeared to be less susceptible (by 1 to 2 orders of magnitude)
to ROPV infection than the undersurfaces of the tongues (unpublished
observations). In addition, the ROPV-induced oral and genital lesions
in adult rabbits appeared to be very immunogenic and often quickly
regressed. Earlier reports had suggested that the ventral lingual site
was more susceptible to ROPV infection than other oral sites
(17). Thus, the use of the athymic mouse xenograft system
provided us with a method to produce high concentrations of infectious
virus, which in turn increased the likelihood of successful infection
of the less susceptible genital mucosal sites.
In summary, we have shown that (i) ROPV can infect rabbit genital
mucosal tissues when transplanted subrenally into athymic mice, (ii)
ROPV can directly infect genital tissues in adult immunocompetent rabbits, and (iii) infected genital tissues produce productive infections. These studies represent the first documented case of ROPV
infection in a mucosal tissue other than in the oral cavity. ROPV
infection of genital tissues may provide a new animal model for the
study of a genital mucosal tissue-targeting PV. Such a laboratory
animal model system will be particularly useful for study of immunity
to PVs following direct infection of genital tissues of intact hosts,
as well as of sexual transmission of PV infections from male to female
and vice versa.
| |
ACKNOWLEDGMENTS |
This work was supported by Public Health Service grants AI35138,
AI37829, and RR07006 and the Jake Gittlen Memorial Golf Tournament.
We thank Martin Pickel for expert technical assistance.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Pathology, The Jake Gittlen Cancer Research Institute, The Milton S. Hershey Medical Center, Pennsylvania State University, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-6185. Fax: (717) 531-5634. E-mail:
ndc1{at}psu.edu.
| |
REFERENCES |
| 1.
|
Bregman, C. L.,
R. S. Hirth,
J. P. Sundberg, and E. F. Christensen.
1987.
Cutaneous neoplasms in dogs associated with canine oral papillomavirus vaccine.
Vet. Pathol.
24:477-487[Abstract].
|
| 2.
|
Campo, M. S.,
M. H. Moar,
W. F. Jarrett, and H. M. Laird.
1980.
Presence and expression of bovine papillomavirus type 4 in tumours of the alimentary canal of cattle and its possible role: a new papillomavirus associated with alimentary cancer in cattle.
Nature
286:180-182[Medline].
|
| 3.
|
Chan, S. Y.,
R. S. Ostrow,
A. J. Faras, and H. U. Bernard.
1997.
Genital papillomaviruses (PVs) and epidermodysplasia verruciformis PVs occur in the same monkey species: implications for PV evolution.
Virology
228:213-217[Medline].
|
| 4.
|
Chandrachud, L. M.,
G. J. Grindlay,
G. M. McGarvie,
B. W. O'Neil,
E. R. Wagner,
W. F. H. Jarrett, and M. S. Campo.
1995.
Vaccination of cattle with the N-terminus of L2 is necessary and sufficient for preventing infection by bovine papillomavirus-4.
Virology
211:204-208[Medline].
|
| 5.
|
Christensen, N. D.,
N. M. Cladel,
C. A. Reed,
L. R. Budgeon,
P. A. Welsh,
S. D. Patrick, and J. W. Kreider.
1996.
Laboratory production of infectious stocks of rabbit oral papillomavirus.
J. Gen. Virol.
77:1793-1798[Abstract/Free Full Text].
|
| 6.
|
Delius, H.,
M. A. Van Ranst,
A. B. Jenson,
H. zur Hausen, and J. P. Sundberg.
1994.
Canine oral papillomavirus genomic sequence: a unique 1.5-kb intervening sequence between the E2 and L2 open reading frames.
Virology
204:447-452[Medline].
|
| 7.
|
DiGiacomo, R. F., and C. J. Mare.
1994.
Rabbit oral papillomavirus, p. 186-187.
In
P. J. Manning, D. H. Ringler, and C. E. Newcomer (ed.), The biology of the laboratory rabbit, 2nd ed. Academic Press, Inc., San Diego, Calif.
|
| 8.
|
Dominguez, J. A.,
E. L. Corella, and A. Auro.
1981.
Oral papillomatosis in two laboratory rabbits in Mexico.
Lab. Anim. Sci.
31:71-73[Medline].
|
| 9.
|
Iwasaki, T.,
H. Maeda,
Y. Kameyama,
M. Moriyama,
S. Kanai, and T. Kurata.
1997.
Presence of a novel hamster oral papillomavirus in dysplastic lesions of hamster lingual mucosa induced by application of dimethylbenzanthracene and excisional wounding: molecular cloning and complete nucleotide sequence.
J. Gen. Virol.
78:1087-1093[Abstract].
|
| 10.
|
Jarrett, W. F. H.,
B. W. O'Neil,
J. M. Gaukroger,
H. M. Laird,
K. T. Smith, and M. S. Campo.
1990.
Studies on vaccination against papillomaviruses: a comparison of purified virus, tumour extract and transformed cells in prophylactic vaccination.
Vet. Rec.
126:449-452[Abstract].
|
| 11.
|
Kloster, B. E.,
D. A. Manias,
R. S. Ostrow,
M. K. Shaver,
S. W. McPherson,
S. R. S. Rangen,
H. Uno, and A. J. Faras.
1988.
Molecular cloning and characterization of the DNA of two papillomaviruses from monkeys.
Virology
166:30-40[Medline].
|
| 12.
|
Kreider, J. W.,
M. K. Howett,
M. H. Stoler,
A. E. Leure-Dupree,
N. L. Lill, and R. J. Zaino.
1987.
Tissue-specific expression of human papillomavirus type 11, p. 215-222.
In
B. M. Steinberg, J. L. Brandsma, and L. B. Taichman (ed.), Cancer cells 5. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
|
| 13.
|
Kreider, J. W.,
M. K. Howett,
S. A. Wolfe,
G. L. Bartlett,
R. J. Zaino,
T. V. Sedlacek, and R. Mortel.
1985.
Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata.
Nature
317:639-641[Medline].
|
| 14.
|
O'Banion, K. M.,
M. E. Cialkowski,
M. E. Reichmann, and J. P. Sundberg.
1988.
Cloning and molecular characterization of an oral papillomavirus of domestic rabbits.
Virology
162:221-231[Medline].
|
| 15.
|
O'Banion, M. K.,
J. P. Sundberg,
A. L. Shima, and M. E. Reichmann.
1987.
Venereal papilloma and papillomavirus in a colobus monkey (Colobus guereza).
Intervirology
28:232-237[Medline].
|
| 16.
|
Ostrow, R. S.,
R. C. McGlennen,
M. K. Shaver,
B. E. Kloster,
D. Houser, and A. J. Faras.
1990.
A rhesus monkey model for sexual transmission of papillomavirus isolated from a squamous cell carcinoma.
Proc. Natl. Acad. Sci. USA
87:8170-8179[Abstract/Free Full Text].
|
| 17.
|
Parsons, R. J., and J. G. Kidd.
1942.
Oral papillomatosis of rabbits: a virus disease.
J. Exp. Med.
77:233-250.
|
| 18.
|
Patel, K. R.,
K. T. Smith, and M. S. Campo.
1987.
The nucleotide sequence and genome organization of bovine papillomavirus type-4.
J. Gen. Virol.
68:2117-2128[Abstract/Free Full Text].
|
| 19.
|
Rangan, S. R.,
A. Gutter,
G. B. Baskin, and D. Anderson.
1980.
Virus associated papillomas in colobus monkeys (Colobus guereza).
Lab. Anim. Sci.
30:885-889[Medline].
|
| 20.
|
Rdzok, E. J.,
N. L. Shipkowitz, and W. R. Richter.
1966.
Rabbit oral papillomatosis: ultrastructure of experimental infection.
Cancer Res.
26:160-165[Abstract/Free Full Text].
|
| 21.
|
Richter, W. R.,
N. L. Shipkowitz, and E. J. Rdzok.
1964.
Oral papillomatosis of the rabbit: an electron microscope study.
Lab. Investig.
13:430-438[Medline].
|
| 22.
|
Shah, A. K.,
R. J. Sawchuk,
A. Gratwohl,
H. Baldomero, and B. Speck.
1988.
Subcutaneous absorption of cyclosporine in rabbits.
Transplant. Proc.
20:710-714[Medline].
|
| 23.
|
Shope, R. E., and E. W. Hurst.
1933.
Infectious papillomatosis of rabbits, with a note on the histopathology.
J. Exp. Med.
58:607-624[Abstract].
|
| 24.
|
Smith, K. T., and M. S. Campo.
1989.
Amplification of specific DNA sequences in C127 mouse cells transformed by bovine papillomavirus type 4.
Oncogene
4:409-413[Medline].
|
| 25.
|
Sundberg, J. P.,
R. E. Junge, and M. O. El Shazly.
1985.
Oral papillomatosis in New Zealand White rabbits.
Am. J. Vet. Res.
46:664-668[Medline].
|
| 26.
|
Weisbroth, S. H., and S. Scher.
1970.
Spontaneous oral papillomatosis in rabbits.
J. Am. Vet. Med. Assoc.
157:1940-1944[Medline].
|
J Virol, June 1998, p. 5239-5244, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Van Doorslaer, K., Rector, A., Jenson, A. B., Sundberg, J. P., Van Ranst, M., Ghim, S.-J.
(2007). Complete genomic characterization of a murine papillomavirus isolated from papillomatous lesions of a European harvest mouse (Micromys minutus). J. Gen. Virol.
88: 1484-1488
[Abstract]
[Full Text]
-
Christensen, N. D., Han, R., Cladel, N. M., Pickel, M. D.
(2001). Combination Treatment with Intralesional Cidofovir and Viral-DNA Vaccination Cures Large Cottontail Rabbit Papillomavirus-Induced Papillomas and Reduces Recurrences. Antimicrob. Agents Chemother.
45: 1201-1209
[Abstract]
[Full Text]
Top
Abstract
Text
