1 Institute of Comparative Medicine, Department of Veterinary Pathology, University of Glasgow Veterinary School, Garscube Estate, Glasgow G61 1QH, UK
2 Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Garscube Estate, Glasgow G61 1QH, UK
Correspondence
L. Nasir
l.nasir{at}vet.gla.ac.uk
![]() |
ABSTRACT |
---|
Published ahead of print on 10 February 2003 as DOI 10.1099/vir.0.18947-0.
![]() |
INTRODUCTION |
---|
|
|
![]() |
Epidemiology |
---|
![]() |
Evidence for virus aetiology |
---|
Although a virus has been suspected as a causative agent (Olson & Cook, 1951; Ragland & Spencer, 1969
), no papillomavirus has been isolated from clinical cases. Studies on a cell line derived from an equine sarcoid (the MC-1 cell line) and on a cell line derived from a tumour induced by inoculation of a combined immunodeficient foal with MC-1 cells (the T-77-4 cell line) revealed the presence of virus particles containing high molecular mass RNA genomes and reverse-transcriptase activity (England et al., 1973
; Fatemi-Nainie et al., 1982
, 1984
; Cheevers et al., 1982
). However, the virus associated with MC-1 cells and their derivatives was a non-oncogenic, replication-defective virus, presumed to be an endogenous equine retrovirus, and a causative relationship between this virus and equine sarcoids was not established (Cheevers et al., 1986
).
![]() |
BPV as the causative agent of sarcoids |
---|
BPV gene expression has been examined in equine sarcoids using RT-PCR and Western blotting. Nasir & Reid (1999) examined 20 equine sarcoids containing BPV type 1 DNA and demonstrated BPV-specific RNA in all samples. Carr et al. (2001b)
analysed 23 sarcoids by Western blot and demonstrated the presence of the BPV E5 protein in all tumours (including one in which the amount of viral DNA was too low for detection), whereas E5 was absent in all of the non-sarcoid samples examined.
Sequence analysis of BPV DNA extracted from sarcoids has revealed the presence of distinct equine sarcoid-specific variants (Otten et al., 1993; Reid et al., 1994
). Reid et al. (1994)
found two minor differences in the sequence of the BPV E5 open reading frame in donkey sarcoids compared with the published bovine sequences. However, another report suggests absolute identity between the BPV E5 sequences in sarcoids and the published BPV sequences (Carr et al., 2001a
).
![]() |
Mechanism of transformation by BPV in cattle |
---|
Some types of papillomavirus can also infect fibroblasts and induce fibro-epithelial tumours, including BPV types 1 and 2, which cause benign fibropapillomas in cattle. Both viruses have a genome of 7900 bp of double-stranded DNA, with at least nine potential reading frames. Like other papillomaviruses, the genome can be split into two principal regions. The early (E) region, encodes the transforming proteins E5, E6 and E7, and the replication and transcription regulatory proteins E1 and E2. The late (L) region encodes the structural proteins of the virus L1 and L2. The early and late regions are separated by a stretch of non-transcribed DNA, called the long control region, which contains the transcriptional promoters and enhancer, the origin of DNA replication and binding sites for numerous cellular transcription factors. During acute virus infection, replication of the virus genome is linked strictly to the state of differentiation of the infected cell. In papilloma formation, for example, the virus infects initially the basal keratinocytes. The early region genes are then expressed in the undifferentiated basal and suprabasal layers. Viral DNA is replicated in the differentiating spinous and granular layers and expression of the late structural proteins is limited to the terminally differentiated cells of the squamous layer, where the new virus particles are encapsidated and released into the environment as the cells die. Initiation of malignant transformation is linked to the deregulated expression of the early virus genes, which results in an uncontrolled proliferation (and loss of differentiation) of the infected cells (Campo, 1997a).
E5 and E6 are the transforming proteins of BPV. The major BPV transforming protein, E5, is a short hydrophobic membrane protein localizing to the Golgi apparatus and other intracellular membranes. It binds to and constitutively activates the platelet-derived growth factor- receptor (PDGF-R) in transformed cells by forming a stable complex with the receptor causing its dimerization and transphosphorylation. The stimulation of the PDGF-R activates a receptor signalling cascade, resulting in an intracellular growth stimulatory signal (DiMaio & Mattoon, 2001
). E5 also binds 16K ductin/subunit c, a component of gap junctions and of the vacuolar ATPase. This interaction is deemed responsible for the downregulation of gap junction intracellular communication with the consequent isolation of the infected cell from its neighbours (Faccini et al., 1996
). Interaction with 16K leads also to alkalinization of the endosomes and the Golgi apparatus (Straight et al., 1995
; Schapiro et al., 2000
), with consequent intracellular retention of MHC class I molecules (Ashrafi et al., 2002
; Marchetti et al., 2002
). The absence of MHC class I from the cell surface would help the infected cells evade host immunosurveillance. Furthermore, E5 activates numerous kinases, including cyclin A-cdk2, MAP, JNK, PI3 and c-Src, thus interfering with proper cell-cycle control and signal transduction cascades (Venuti & Campo, 2002
).
The E6 protein is found localized in membrane and nuclear fractions and contains two highly conserved zinc finger domains typical of DNA-binding transcription activator proteins. However, cell transformation by E6 appears to be independent of its transcription transactivation function (Ned et al., 1997). While HPV E6 binds and stimulates degradation of p53, BPV E6 does not (Scheffner et al., 1990
; Rapp et al., 1999
). Instead, the transformational ability of BPV E6 is linked to its ability to bind ERC-55/E6BP (Chen et al., 1995
) and in part, CBP/p300 (Zimmermann et al., 2000
). ERC-55/E6BP is a calcium-binding protein and CBP/p300 is a transcriptional co-activator and binding of these proteins by E6 would interfere with normal cell functions. E6 also binds the focal adhesion protein paxillin (Tong & Howley, 1997
; Tong et al., 1997
; Vande Pol et al., 1998
) and the
subunit of the clathrin adaptor complex AP-1 (Tong et al., 1998
). These interactions lead to disruption of cytoskeleton and vesicular traffic pathways, respectively. The cytoskeleton is vital for the maintenance of cellular morphology, motility, division and cellcell and cellmatrix interactions and the AP-1 complex plays an important role in the control of cell proliferation and differentiation.
![]() |
BPV and the pathogenesis of equine sarcoids |
---|
Recently, it has emerged that intra-type sequence variation occurs within papillomavirus types, which can influence the cellular location and function of the oncoproteins and consequently affect the pathogenesis and transforming ability of the virus (Giannoudis & Herrington, 2001). Using sequence analysis of BPV DNA isolates extracted from sarcoids, the presence of distinct equine sarcoid-specific variants of BPV has been detected (Otten et al., 1993
; Reid et al., 1994
). The sequence changes in the E5 protein reported by Reid et al. (1994)
suggest the possibility that these changes are contributory factors to the pathogenesis of the disease. As found for HPV, these sequence changes could affect the expression and function of the early virus proteins and may explain the different pathogenesis of the equine sarcoid compared to papillomas induced by BPV in cattle. However, this remains to be established.
![]() |
Other factors involved in sarcoid development |
---|
Other research has shown a strong association between risk of sarcoid development and certain alleles of the class II region of the equine MHC. When the frequency of equine MHC class II haplotypes was examined in thoroughbred and standardbred horses in the USA, it was found that there was a highly significant association between the MHC class II haplotypes W3 and B1 in the thoroughbred population. These findings were the first to suggest an association between predisposition to sarcoids and particular MHC haplotypes (Meredith et al., 1986) and were later confirmed by subsequent studies. It was found that the W13 haplotype is associated strongly with sarcoids in Swedish halfbreds (Brostrom et al., 1988
) and Swiss Warmbloods (Gerber et al., 1988
). A further Swedish study showed that there is an association between increased recurrence of sarcoids following surgery with the W13 haplotype and association between early onset of sarcoids and the A5 haplotype (Brostrom, 1995
).
The underlying mechanisms associated with this genetic predisposition are unclear. Specific MHC class II alleles may be associated with an impaired immune response to BPV and/or other tumour-associated sarcoid antigens, as defined in the MC-1 sarcoid cell line (Watson & Larson, 1974; Brostrom, 1989
). Certainly, there is an association between certain MHC class II genes and the development of tumours induced in rabbits by CRPV (Han et al., 1992
) and in human cervical carcinoma associated with HPV types 16 or 18 (Wank & Thomssen, 1991
; Breitburd et al., 1996
).
The role of the immune response in determining the outcome of papillomavirus infections is well known. In most cases, regression of papillomavirus lesions occurs following activation of the host immune response. However, several immune evasion mechanisms that may contribute to persistence and malignant progression of papillomavirus-associated disease have been described (O'Brien & Campo, 2002). Sarcoids are non-regressing, unlike many other lesions caused by papillomavirus infection. This suggests that expression of the BPV proteins in equine cells may evoke similar immune evasion mechanisms. In particular, the expression of BPV E5, which downregulates MHC class I expression (Ashrafi et al., 2002
; Marchetti et al., 2002
) and hence may affect the ability of the infected cells to be detected by cytotoxic T lymphocytes, may be a major factor in BPV persistence. In addition, sarcoids, although benign, are recurrent lesions, reminiscent of recurrent respiratory papillomatosis in humans caused by HPV types 6 or 11. The persistence of papillomaviruses in these laryngeal lesions and recurrence of disease has been attributed to a downregulation of the transporter associated with antigen presentation (TAP) genes, causing a subsequent loss of the MHC class I expression (Vambutas et al., 2001
). Very little is known about the immune response to equine sarcoids and hence the significance of these evasion mechanisms to prolonged BPV persistence is not known.
Several investigators have examined the role of the tumour suppressor gene p53 in equine sarcoids. Bucher et al. (1996) failed to detect p53 gene mutations in equine sarcoid tumours, suggesting that p53 does not play a significant role in the pathogenesis of sarcoids. This was corroborated further by an investigation of sarcoids in donkeys (Nasir et al., 1999
). However, more recently, aberrant perinuclear localization of p53 has been demonstrated in 44 % of equine sarcoid lesions (Martens et al., 2001b
), suggesting that mutational independent inactivation of p53 occurs commonly in sarcoids; the significance of these finding remains to be elucidated.
![]() |
Possible means of transmission of infection |
---|
![]() |
Treatment of sarcoids |
---|
Efficacy of different treatments is difficult to assess because most studies have not been controlled and are based on referral populations of horses treated at major clinics or veterinary hospitals. Such referral populations may not represent the overall tumour population in the field but a subset of fast growing, recurrent or multiple tumours that veterinary practitioners in the field have been unable to treat successfully. Conversely, many private practitioners treat sarcoids successfully by a policy of non-intervention, which again may represent a specific population of sarcoids that remain quiescent or the rare spontaneous regressors and there is some anecdotal evidence for this (Goodrich et al., 1998).
Sarcoids frequently display hyperproliferation or recurrence if treated by surgical excision, which has led some to speculate that this could be due to activation of latent BPV in apparently normal tissue surrounding the lesion. Martens et al. (2001a) used PCR to test for BPV in sarcoids removed by surgery and also tested apparently normal skin around the sarcoids. They found BPV in all of the sarcoids and also in the surrounding normal skin. The frequency of detection of BPV in the normal skin decreased as the resection margin was increased. They also found that animals with a surgical margin containing BPV had a greater probability to show local recurrence. These observations agree with the results of a study that examined the inducement of tumour development by trauma in an experimental model. Siegsmund et al. (1991)
used a laboratory strain of the rodent Mastomys natalensis, which carries an endogenous latent papillomavirus (MnPV), to show that when the skin of these animals was irritated by scratching with glasspaper, hyperproliferation of the epidermis and amplification of viral DNA occurred, with virus-producing papillomas induced in 27 % of the animals.
![]() |
Implications of BPV infection in diagnosis and therapy |
---|
However, the association of a causative virus agent does raise the possibility of employing antiviral therapies in the treatment of sarcoids, including vaccination against BPV in populations with a high incidence of sarcoids, where, for example, a large number of animals are stabled together for long periods of time. We have shown previously in cattle that prophylactic vaccination against the virus capsid proteins of BPV can prevent infection and disease and therapeutic vaccination against the E7 protein can stimulate regression of established papillomas (Campo et al., 1993; Jarrett et al., 1991
), hence supporting the feasibility of vaccination against BPV to reduce or eliminate disease (reviewed by Campo, 1997b
). It has been suggested recently that the E5 protein would be suitable as a target antigen for therapeutic vaccination, both as a membrane-associated and therefore, immune-accessible protein, and because of its probable importance in the pathogenesis of sarcoids (Carr et al., 2001a
). However, considerable research would be needed in order to determine the validity of such an approach.
![]() |
CONCLUSION |
---|
![]() |
ACKNOWLEDGEMENTS |
---|
![]() |
REFERENCES |
---|
Angelos, J. A., Oppenheim, Y., Rebhun, W., Mohammed, H. & Antczak, D. F. (1988). Evaluation of breed as a risk factor for sarcoid and uveitis in horses. Anim Genet 19, 417425.[Medline]
Angelos, J. A., Marti, E., Lazary, S. & Carmichael, L. E. (1991). Characterization of BPV-like DNA in equine sarcoids. Arch Virol 119, 95109.[Medline]
Ashrafi, G. H., Tsirimonaki, E., Marchetti, B., O'Brien, P. M., Sibbet, G. J., Andrew, L. & Campo, M. S. (2002). Down-regulation of MHC class I by bovine papillomavirus E5 oncoproteins. Oncogene 21, 248259.[CrossRef][Medline]
Bloch, N., Breen, M. & Spradbrow, P. B. (1994). Genomic sequences of bovine papillomaviruses in formalin-fixed sarcoids from Australian horses revealed by polymerase chain reaction. Vet Microbiol 41, 163172.[CrossRef][Medline]
Boiron, M., Levy, J. P., Thomas, M., Freidman, J. C. & Bernard, J. C. (1964). Some properties of bovine papillomavirus. Nature 201, 423.[Medline]
Breitburd, F., Ramoz, N., Salmon, J. & Orth, G. (1996). HLA control in the progression of human papillomavirus infections. Semin Cancer Biol 7, 359371.[CrossRef][Medline]
Brostrom, H. (1989). Surface antigens on equine sarcoid cells and normal dermal fibroblasts as assessed by xenogenic antisera. Res Vet Sci 46, 172179.[Medline]
Brostrom, H. (1995). Equine sarcoids. A clinical and epidemiological study in relation to equine leucocyte antigens (ELA). Acta Vet Scand 36, 223236.[Medline]
Brostrom, H., Bredberg-Raden, U., England, J., Obel, N. & Perlmann, P. (1979). Cell-mediated immunity in horses with sarcoid tumours against sarcoid cells in vitro. Am J Vet Res 40, 17011706.[Medline]
Brostrom, H., Fahlbrink, E., Dubath, M.-L. & Lazary, S. (1988). Association between equine leucocyte antigens (ELA) and equine sarcoid tumours in the population of Swedish halfbreds and some of their families. Vet Immunol Immunopathol 19, 215223.[CrossRef][Medline]
Bucher, K., Szalai, G., Marti, E., Griot-Wenk, M. E., Lazary, S. & Pauli, U. (1996). Tumour suppressor gene p53 in the horse: identification, cloning, sequencing and a possible role in the pathogenesis of equine sarcoid. Res Vet Sci 61, 114119.[Medline]
Campo, M. S. (1997a). Bovine papillomavirus and cancer. Vet J 154, 175188.[Medline]
Campo, M. S. (1997b). Vaccination against papillomavirus in cattle. Clin Dermatol 15, 275283.[CrossRef][Medline]
Campo, M. S., Grindlay, G. J., O'Neil, B. W., Chandrachud, L. M., McGarvie, G. M. & Jarrett, W. F. H. (1993). Prophylactic and therapeutic vaccination against a mucosal papillomavirus. J Gen Virol 74, 945953.[Abstract]
Carr, E. A., Theon, A. P., Madewell, B. R., Hitchcock, M. E., Schlegel, R. & Schiller, J. T. (2001a). Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses. Am J Vet Res 62, 12121217.[Medline]
Carr, E. A., Theon, A. P., Madewell, B. R., Griffey, S. M. & Hitchcock, M. E. (2001b). Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from horses with and without sarcoids in the western United States. Am J Vet Res 62, 741744.[Medline]
Cheevers, W. P., Roberson, S. M., Brassfield, A. L., Davis, W. C. & Crawford, T. B. (1982). Isolation of a retrovirus from cultured equine sarcoid tumour cells. Am J Vet Res 43, 804806.[Medline]
Cheevers, W. P., Fatemi-Nainie, S. & Anderson, L. W. (1986). Spontaneous expression of an endogenous retrovirus by the equine sarcoid-derived MC-1 cell line. Am J Vet Res 47, 5052.[Medline]
Chen, J. J., Reid, C. E., Band, V. & Androphy, E. J. (1995). Interaction of papillomavirus E6 oncoproteins with a putative calcium-binding protein. Science 269, 529531.[Medline]
DiMaio, D. & Mattoon, D. (2001). Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene 20, 78667873.[CrossRef][Medline]
England, J. J., Watson, R. E., Jr & Larson, K. A. (1973). Virus-like particles in an equine sarcoid cell line. Am J Vet Res 34, 16011603.[Medline]
Faccini, A. M., Cairney, M., Ashrafi, G. H., Finbow, M. E., Campo, M. S. & Pitts, J. D. (1996). The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts. J Virol 70, 90419045.[Abstract]
Fatemi-Nainie, S., Anderson, L. W. & Cheevers, W. P. (1982). Identification of a transforming retrovirus from cultured equine dermal fibrosarcoma. Virology 120, 490494.[Medline]
Fatemi-Nainie, S., Anderson, L. W. & Cheevers, W. P. (1984). Culture characteristics and tumorigenicity of the equine sarcoid-derived MC-1 cell line. Am J Vet Res 45, 11051108.[Medline]
Gerber, H., Dubath, M.-L. & Lazary, L. (1988). Association between predisposition to equine sarcoid and MHC in multiple-case families. In Equine Infectious Diseases, Proceedings of the Fifth International Conference, pp 272277. Edited by D. G. Powel. Kentucky: University Press.
Giannoudis, A. & Herrington, C. S. (2001). Human papillomavirus variants and squamous neoplasia of the cervix. J Pathol 193, 295302.[CrossRef][Medline]
Goldschmidt, M. H. & Hendrick, M. J. (2002). Equine sarcoid. In Tumours in Domestic Animals, 4th edition, pp 8889. Edited by D. J. Meuten. Iowa: Iowa State University Press.
Goodrich, L., Gerber, H., Marti, E. & Antczack, D. F. (1998). Equine sarcoids. Vet Clin N Am Equine Prac 14, 607623.
Han, R., Breitburd, F., Marche, P. N. & Orth, G. (1992). Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature 356, 6668.[CrossRef][Medline]
IARC. (1995). Monographs on the evaluation of carcinogenic risk to humans. In Human Papillomaviruses. World Health Organization International Agency for Research on Cancer.
Jackson, C. (1936). The incidence and pathology of tumours of domesticated animals in South Africa. Onderstepoort J Vet Sci Anim Ind 6, 378385.
James, V. S. (1968). A family tendency to equine sarcoid. SW Vet 21, 235236.
Jarrett, W. F. H., Smith, K. T., O'Neil, B. W., Gaukrodger, J. M., Chandrachud, L. M., Grindlay, G. J., McGarvie, G. M. & Campo, M. S. (1991). Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins. Virology 184, 3342.[Medline]
Kemp-Symonds, J. G. (2000). The detection and sequencing of bovine papillomavirus type 1 and 2 DNA from Musca autumnalis (Diptera: Muscidae) face flies infesting sarcoid-affected horses. MSc thesis, Royal Veterinary College, London, UK.
Knottenbelt, D. C. & Walker, J. A. (1994). Treatment of the equine sarcoid. Equine Vet Educ 6, 7275.
Lancaster, W. D. (1981). Apparent lack of integration of bovine papillomavirus DNA in virus-induced equine and bovine tumor cells and virus-transformed mouse cells. Virology 108, 251255.[Medline]
Lancaster, W. D., Theilen, G. H. & Olson, C. (1979). Hybridization of bovine papilloma virus type 1 and type 2 DNA to DNA from virus-induced hamster tumors and naturally occurring equine tumors. Intervirology 11, 227233.[Medline]
Lazary, S., Gerber, H., Glatt, P. A. & Straub, R. (1985). Equine leucocyte antigens in sarcoid-affected horses. Equine Vet J 17, 283286.[Medline]
Lory, S., von Tscharner, C., Marti, E., Bestetti, G., Grimm, S. & Waldvogel, A. (1993). In situ hybridisation of equine sarcoids with bovine papilloma virus. Vet Rec 132, 132133.[Medline]
Marchetti, B., Ashrafi, G. H., Tsirimonaki, E., O'Brien, P. M. & Campo, M. S. (2002). The papillomavirus oncoprotein E5 retains the major histocompatibility class I in the Golgi apparatus and prevents its transport to the cell surface. Oncogene 21, 78087816.[CrossRef][Medline]
Martens, A., De Moor, A., Demeulemeester, J. & Peelman, L. (2001a). Polymerase chain reaction analysis of the surgical margins of equine sarcoids for bovine papilloma virus DNA. Vet Surg 30, 460467.[CrossRef][Medline]
Martens, A., De Moor, A. & Ducatelle, R. (2001b). PCR detection of bovine papilloma virus DNA in superficial swabs and scrapings from equine sarcoids. Vet J 161, 280286.[CrossRef][Medline]
Marti, E., Lazary, S., Antczak, D. F. & Gerber, H. (1993). Report of the first international workshop on equine sarcoid. Equine Vet J 25, 397407.[Medline]
Meredith, D., Elser, A. H., Wolf, B., Soma, L. R., Donawick, W. J. & Lazary, S. (1986). Equine leukocyte antigens: relationships with sarcoid tumors and laminitis in two pure breeds. Immunogenetics 23, 221225.[Medline]
Mohammed, H. O., Rebhun, W. C. & Antczack, D. F. (1992). Factors associated with the risk of developing sarcoid tumours in horses. Equine Vet J 24, 165168.[Medline]
Nasir, L. & Reid, S. W. J. (1999). Bovine papillomaviral gene expression in equine sarcoid tumours. Virus Res 61, 171175.[CrossRef][Medline]
Nasir, L., McFarlane, S. T., Torrontegui, B. O. & Reid, S. W. J. (1997). Screening for bovine papillomavirus in peripheral blood cells of donkeys with and without sarcoids. Res Vet Sci 63, 289290.[Medline]
Nasir, L., McFarlane, S. T. & Reid. (1999). Mutational status of the tumour suppressor gene (p53) in donkey sarcoid tumours. Vet J 157, 99101.[CrossRef][Medline]
Ned, R., Allen, S. & Vande Pol, S. (1997). Transformation by bovine papillomavirus type 1 E6 is independent of transcriptional activation by E6. J Virol 71, 48664870.[Abstract]
O'Brien, P. M. & Campo, M. S. (2002). Evasion of host immunity directed by papillomavirus-encoded proteins. Virus Res 88, 103117.[CrossRef][Medline]
Olson, C., Jr & Cook, R. H. (1951). Cutaneous sarcoma-like lesions of the horse caused by the agent of bovine papilloma. Proc Soc Exp Biol Med 77, 281284.
Otten, N., Von Tscharner, C., Lazary, S., Antczak, D. F. & Gerber, H. (1993). DNA of bovine papillomavirus type 1 and 2 in equine sarcoids: PCR detection and direct sequencing. Arch Virol 132, 121131.[Medline]
Pascoe, R. R. & Summers, P. M. (1981). Clinical survey of tumours and tumour-like lesions in horses in south east Queensland. Equine Vet J 13, 235239.[Medline]
Ragland, W. L. & Spencer, G. R. (1969). Attempts to relate bovine papilloma virus to the cause of equine sarcoid: equidae inoculated intradermally with bovine papilloma virus. Am J Vet Res 30, 743752.[Medline]
Ragland, W. L., Keown, G. H. & Gorham. (1966). An epizootic of equine sarcoid. Nature 210, 1399.[Medline]
Ragland, W. H., Keown, G. H. & Spencer, G. R. (1970). Equine sarcoid. Equine Vet J 2, 211.
Rapp, L., Liu, Y., Hong, Y., Androphy, E. J. & Chen, J. J. (1999). The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor -induced apoptosis. Oncogene 18, 607615.[CrossRef][Medline]
Reid, S. W. J. (1992). The equine sarcoid: molecular and epidemiological studies in Equus asinus. PhD thesis, University of Glasgow, Glasgow, UK.
Reid, S. W. J. & Mohammed, H. O. (1997). Longitudinal and cross-sectional studies to evaluate the risk of sarcoid associated with castration. Can J Vet Res 61, 8993.[Medline]
Reid, S. W. J., Smith, K. T. & Jarrett, W. H. F. (1994). Detection, cloning and characterisation of papillomaviral DNA present in sarcoid tumours of Equus asinus. Vet Rec 135, 430432.[Medline]
Robl, M. G. & Olson, C. (1968). Oncogenic action of bovine papilloma virus in hamsters. Cancer Res 28, 15961604.[Medline]
Schapiro, F., Sparkowski, J., Adduci, A., Suprynowicz, F., Schlegel, R. & Grinstein, S. (2000). Golgi alkalinization by the papillomavirus E5 oncoprotein. J Cell Biol 148, 305315.
Scheffner, M., Werness, B. A., Huibregtse J. M., Levine, A. J. & Howley, P. M. (1990). The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 11291136.[Medline]
Shope, R. E. (1933). Infectious papillomatosis of rabbits; with a note on the histopathology. J Exp Med 58, 607624.
Siegsmund, M., Wayss, K. & Amtmann, E. (1991). Activation of latent papillomavirus genomes by chronic mechanical irritation. J Gen Virol 72, 27872789.[Abstract]
Sousa, R., Dostatni, N. & Yaniv, M. (1990). Control of papillomavirus gene expression. Biochim Biophys Acta 1032, 1937.[Medline]
Straight, S. W., Herman, B. & McCance, D. J. (1995). The E5 oncoprotein of human papillomavirus type 16 inhibits the acidification of endosomes in human keratinocytes. J Virol 69, 31853192.[Abstract]
Sundberg, J. P., Burnstein, T., Page, E. H., Kirkham, W. W. & Robinson, F. R. (1977). Neoplasms of Equidae. J Am Vet Med Assoc 170, 150152.[Medline]
Syverton, T. J. (1952). The pathogenesis of the rabbit papilloma-to-carcinoma sequence. Ann N Y Acad Sci 54, 11261140.[Medline]
Thomsett, L. R. (1979). Skin diseases of the horse. In Pract 1, 1526.
Tong, X. & Howley, P. M. (1997). The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci U S A 94, 44124417.
Tong, X., Salgia, R., Li, J. L., Griffin, J. D. & Howley, P. M. (1997). The bovine papillomavirus E6 protein binds to the LD motif repeats of paxillin and blocks its interaction with vinculin and the focal adhesion kinase. J Biol Chem 272, 3337333376.
Tong, X., Boll, W., Kirchhausen, T. & Howley, P. M. (1998). Interaction of the bovine papillomavirus E6 protein with the clathrin adaptor complex AP-1. J Virol 72, 476482.
Torrontegui, B. O. & Reid, S. J. (1994). Clinical and pathological epidemiology of the equine sarcoid in a referral population. Equine Vet Educ 6, 8588.
Trenfield, K., Spradbrow, P. B. & Vanselow, B. (1985). Sequences of papillomavirus DNA in equine sarcoids. Equine Vet J 17, 449452.[Medline]
Vambutas, A., DeVoti, J., Pinn, W., Steinberg, B. M. & Bonagura, V. R. (2001). Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the reduction of ATP-dependent peptide transport. Clin Immunol 101, 9499.[CrossRef][Medline]
Vande Pol, S. B., Brown, M. C. & Turner, C. E. (1998). Association of bovine papillomavirus type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16, 4352.[CrossRef][Medline]
Venuti, A. & Campo, M. S. (2002). The E5 protein of Papillomaviruses. In Progress in Medical Virology: Papillomaviruses, pp. 141162. Edited by D. J. McCance. Iowa: Iowa State Press.
Voss, J. L. (1969). Transmission of equine sarcoid. Am J Vet Res 30, 183191.[Medline]
Wank, R. & Thomssen, C. (1991). High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 352, 723725.[CrossRef][Medline]
Watson, R. E., Jr & Larson, K. A. (1974). Detection of tumor-specific antigens in an equine sarcoid cell line. Infect Immun 9, 714718.[Medline]
Zimmermann, H., Koh, C. H., Degenkolbe, R., O'Connor, M. J., Muller, A., Steger, G., Chen, J. J., Lui, Y., Androphy, E. & Bernard, H. U. (2000). Interaction with CBP/p300 enables the bovine papillomavirus type 1 E6 oncoprotein to downregulate CBP/p300-mediated transactivation by p53. J Gen Virol 81, 26172623.
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
J MED MICROBIOL | ALL SGM JOURNALS |