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W F Jarrett

Publications and source records attributed to W F Jarrett.

At least 19 recordsLinked to original sources
PubMed1995

Vaccination of cattle with the N-terminus of L2 is necessary and sufficient for preventing infection by bovine papillomavirus-4.

We have previously shown that cattle vaccinated with L2, the minor structural protein of bovine papillomavirus-4 (BPV-4), do not develop alimentary papillomas upon challenge with BPV-4. Analysis of the B and T cell response in L2-vaccinated animals showed that the majority of the response was directed against the N-terminus and C-terminus of L2 with little response against the middle portion. Cattle were vaccinated with the N-terminus or the C-terminus of L2. The animals vaccinated with the N-terminus were completely protected from viral challenge, whereas the animals vaccinated with the C-terminus were not. Further analysis with synthetic overlapping peptides spanning the entire N-terminus mapped a B cell immunodominant epitope at amino acid 101-120. This epitope was recognised by all vaccinated animals.

Amino Acid Sequence↗
PubMed1995

T cell responses to BPV-4 E7 during infection and mapping of T cell epitopes.

Vaccination of cattle with the recombinant E7 protein of bovine papillomavirus type 4 (BPV-4) prior to BPV-4 infection has been shown to retard development of papillomas and accelerate their regression. To understand the mechanism of regression we have measured proliferation of peripheral blood mononuclear cells (PBM) to E7 in vitro during the course of BPV-4 infection in both vaccinated and nonvaccinated cattle. In vaccinated cattle, T cells specific for E7 could be detected at high levels shortly after challenge, whereas in nonvaccinated cattle low responses of E7-specific T cells could be detected in only a few animals at the late stages of papilloma development. Using short overlapping synthetic peptides corresponding to the E7 protein, three T cell epitopes have been identified. T1 (aa 31-59) was immunodominant and T2 (aa 70-88) and T3 (aa21-40) were minor epitopes.

Amino Acid Sequence↗
PubMed1994

Detection, cloning and characterisation of papillomaviral DNA present in sarcoid tumours of Equus asinus.

Molecular investigations on 18 naturally occurring sarcoid tumors removed from donkeys identified papillomaviral DNA homologous to bovine papillomavirus (BPV)-2 DNA under stringent conditions, in all the samples. Restriction endonuclease analysis of 15 of the tumours demonstrated papillomaviral DNA similar to BPV-1 and BPV-2. The type of DNA was not specific to either the site or the type of lesion. The analysis of the nucleotide base sequence of a cloned papillomaviral element from a sarcoid showed that the isolate was 96 and 98 per cent homologous to BPV-1 in the L1 and E5 open reading frames, respectively. It was concluded that the disease in the donkey is similar to that in the horse and that the E5 open reading frame may be involved in oncogenesis in the sarcoid.

Animals↗
PubMed1994

Vaccination against cutaneous and mucosal papillomavirus in cattle.

Viruses are responsible for approximately 15% of human cancer worldwide. Human papillomavirus and hepatitis B virus are the recognized agents of cervical and liver cancer, respectively, which together constitute 80% of all virally induced cancers. If measures could be found to bring viral infection under control, a great proportion of human cancer would be greatly reduced. Experimental vaccines are being developed against papillomavirus. In principle two different types of vaccine can be envisaged: prophylactic vaccines that would elicit virus-neutralizing antibodies and would prevent infection and therapeutic vaccines that would induce regression of established lesions before progression to malignancy took place. The research on vaccines against human papillomavirus is hampered by the difficulties encountered in growing the virus in tissue culture and by the unacceptable nature of experimentation in humans. Effective vaccines, both natural and genetically engineered, have been developed against bovine papillomavirus and cottontail rabbit papillomavirus. The success obtained with the animal models supports the optimistic prediction that in the relatively near future vaccines will be available against the most problematic or potentially dangerous forms of papillomatosis in humans.

Animals↗
PubMed1994

Humoral immune response to the E7 protein of bovine papillomavirus type 4 and identification of B-cell epitopes.

We have previously vaccinated cattle with E7, the major transforming protein of bovine papillomavirus-4, prior to homologous virus challenge. This retarded the development of papillomas and promoted their early regression compared to control animals. To understand the mechanism for this regression, we have studied the B and T cell response in vaccinated animals and compared it to that of non-vaccinated, virus-infected animals. The B cell response is reported here. The development of E7 IgG antibodies was detected after vaccination and before viral challenge, indicating that vaccine E7 is effectively presented to the immune system. In vaccinated animals titres of E7 antibodies remained high 10 weeks after viral challenge, whereas E7 antibodies in control animals were not detectable until 13 weeks post-viral challenge. Further analysis with synthetic overlapping peptides spanning the entire E7 protein mapped major immunodominant epitopes in the N and C termini of the protein and a minor epitope in the middle of the protein.

Amino Acid Sequence↗
PubMed1994

Latent papillomavirus infection in cattle.

During a long term experiment designed to identify the contribution of bovine papillomavirus type 4 (BPV-4), environmental mutagens and immunosuppressants to the development of carcinomas of the upper alimentary tract of cattle, there was evidence of latent papillomavirus infection. Papillomatosis-free animals, when immunosuppressed either by feeding bracken fern or by azathioprine treatment, developed skin warts containing either BPV-1 or BPV-2. Skin warts appeared also in an immunocompetent animal at sites of damaged skin. It was concluded that the animals harboured latent papillomavirus which was reactivated by immunosuppression and/or physical trauma, causing skin warts. Papillomavirus DNA was also detected in lymphocytes of both experimental and control animals, suggesting that one of the sites of latency may be the circulating lymphocyte.

Animals↗
PubMed1994

Experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle.

Bovine papillomavirus type 4 (BPV-4) is the aetiological agent of epithelial papillomas of the upper alimentary canal in cattle. These benign tumours can become a focus for transformation to squamous cell carcinomas in animals feeding on bracken fern. Strong epidemiological evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and mutagenic and immunosuppressing chemicals present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower intestine and bracken-grazing animals are also heavily immunosuppressed. To elucidate the individual roles and the concerted action of the viral and chemical factors involved in tumorigenesis and malignant conversion, we attempted to reproduce experimentally the cancer syndrome observed in the field. Florid persistent papillomatosis of the upper alimentary canal was reproduced in animals infected with BPV-4 and immunosuppressed either by a diet of bracken or by treatment with azathioprine; cancer of the upper alimentary tract or of the lower intestine developed only in animals infected with virus and fed on bracken fern. As in field cases, BPV-4 DNA was detected in papillomas but not in cancers. We conclude that immunosuppression is necessary for persistence and spread of viral papillomas, that the fern mutagens are responsible for neoplastic conversion of papilloma cells, and that continuous expression of viral functions is not required for the maintenance of the malignant state.

Animals↗
PubMed1993

Interaction between bovine papillomavirus type 4 and cocarcinogens in the production of malignant tumours.

Bovine fetal palatine tissue infected with bovine papillomavirus type 4 (BPV-4) was implanted subcutaneously in athymic nude mice. The implants developed into cysts containing papillomas essentially the same as those in the natural host. In order to investigate the interaction of cocarcinogens with BPV-4 in cell transformation, the virus-infected implants were exposed in vivo to either the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the tumour initiator 7,12-dimethylbenz[a]-anthracene (DMBA). Papillomas were detected in a greater number of infected implants in the presence of either TPA or DMBA than in the absence of either of these chemicals indicating interaction between the virus and these two agents. Moreover, malignantly transformed cells arose with high frequency from infected implants that had been exposed to either chemical. In the presence of chemical and absence of virus or vice versa no neoplastic changes were seen histologically, indicating that cooperation between virus and cocarcinogen is required for transformation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Prophylactic and therapeutic vaccination against a mucosal papillomavirus.

Papillomaviruses are ubiquitous DNA viruses affecting humans and animals and causing a variety of tumours of mucosal and cutaneous epithelia. Some of these lesions, particularly those affecting mucosal epithelia, can progress to squamous cell carcinomas. Prevention or cure of viral infection would ultimately lead to a decrease in the incidence of papillomavirus-associated cancers. Using recombinant proteins, we have developed prophylactic and therapeutic vaccines against bovine papillomavirus type 4, a mucosal papillomavirus implicated in cancer of the alimentary canal in cattle; similar possibilities exist for the human mucosal papillomaviruses.

Animals↗
PubMed1992

Association of bovine papillomavirus type 2 and bracken fern with bladder cancer in cattle.

The bladder cancer syndrome that often accompanies chronic enzootic hematuria in cattle grazing on pastures infested by bracken fern has been experimentally reproduced in animals fed a diet of bracken. The experimentally induced tumors were histologically and pathologically indistinguishable from the naturally occurring ones and comprised two main types: (a) carcinoma of the urothelium identical to that seen in humans; and (b) hemangioendotheliomas of the subjacent capillaries. Often the two types of tumor occurred together in the same bladder. In animals experimentally immunosuppressed with azathioprine "bracken type" hemangiomas developed in the bladder lining. DNA of bovine papillomavirus (BPV) type 2 was found in 46% (7 of 15) of the natural cancer cases and in 69% (9 of 13) of the experimentally induced lesions, independently of histological type and including the hemangiomas of the azathioprine-treated animals, suggesting a close association between BPV and bovine bladder neoplasia. Moreover, BPV-2 DNA was found in experimental animals that had not been inoculated with BPV at all or had been inoculated with a different BPV type and had been kept in isolation, suggesting that BPV can persist in a latent state and be activated when the animal is exposed to the bracken cocarcinogens and to immunosuppressants.

Animals↗
PubMed1991

Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins.

The L1 and L2 proteins of BPV-2 have been produced in Escherichia coli as beta-galactosidase fusion proteins. The fusion proteins have been used to vaccinate calves both prophylactically and therapeutically. The L1 fusion protein prevented tumor formation when administered before challenge with BPV-2, while the L2 fusion protein was very effective in promoting tumor rejection, independently from whether it was administered before or after challenge. Animals vaccinated with L1, but not with L2, responded rapidly with production of serum neutralizing antibodies, showing that this peptide contains B-cell-specific epitopes. The massive infiltration of lymphocytes in the tumors of L2-vaccinated animals suggests that the peptide contains epitopes specific for T-cells. The two structural proteins of BPV-2 therefore interact with both efferent arms of the immune system, and this observation allows the choice between two different types of antiviral vaccination.

Animals↗
PubMed1991

Malignant transformation of a papilloma induced by bovine papillomavirus type 4 in the nude mouse renal capsule.

A papillomatous cyst was induced by implanting bovine foetal palate epithelium, infected in vitro with bovine papillomavirus type 4 (BPV-4), beneath the renal capsule of a nude mouse. The benign tumour underwent malignant progression, developing into a squamous cell carcinoma with metastatic deposits in the spleen. The bovine origin of both the renal and splenic cancers was confirmed by the presence of bovine major histocompatibility complex class I antigens in the cancer cells and by sequencing the Harvey-ras 1 gene, which was shown to be of bovine origin. BPV-4 DNA was present in the residual papillomatous fronds of the renal cancer, but was absent from the carcinoma proper and for the splenic metastasis. These results confirm that BPV-4 is a carcinogenic agent and that its genetic information is not necessary for the maintenance of the malignant phenotype. Moreover the system provides the opportunity to investigate the role of viral and chemical carcinogens in an experimental system.

Animals↗
PubMed1990

Studies on vaccination against papillomaviruses: the immunity after infection and vaccination with bovine papillomaviruses of different types.

Calves, free of antibodies to bovine papillomaviruses (BPV), were reared in isolation. One was infected with BPV-2, developed tumours and was resistant to homologous reinfection. Groups of calves were infected with BPV-2, BPV-5 or BPV-6; they all developed and subsequently rejected type-specific tumours. They were then infected with BPV-4; they were not immune and oral papillomas were induced. Groups of animals were vaccinated by intramuscular preparations of purified BPV-4 and BPV-6 and were challenged with homologous virus; all were immune to reinfection. An earlier experiment had shown this to be true for BPV-2. Two calves, immune to BPV-6, were not immune to BPV-1. These experiments, although they do not cover all the possibilities of reciprocal immunisation and challenge, indicate that prophylactic immunity to a range of papillomaviruses is type-specific. This is the first clear demonstration of this phenomenon in the papillomavirus group.

Animals↗
PubMed1990

Studies on vaccination against papillomaviruses: a comparison of purified virus, tumour extract and transformed cells in prophylactic vaccination.

Calves were vaccinated with two preparations made from one cutaneous fibropapilloma induced by bovine papillomavirus type 2 (BPV-2). One vaccine consisted of homogenised tumour; the other contained purified virus only. Both produced resistance to a heavy challenge infection of BPV-2. One calf in the vaccinated group developed a small tumour and rejected it earlier than the control calves. It would appear likely that the prophylactic immune response was induced by viral structural proteins only and that tumour-specific antigens are unnecessary. Bovine fibroblasts were transformed in vitro by BPV-2 and administered as a vaccine; immunity was not induced.

Animals↗
PubMed1990

The Harvey ras 1 gene is activated in papillomavirus-associated carcinomas of the upper alimentary canal in cattle.

The possible activation of ras sequences in papillomavirus-associated carcinomas of the upper alimentary canal of cattle was investigated by restriction enzyme and hybridization analysis, and by DNA-mediated transformation of NIH3T3 cells. In three cancers, a squamous cell carcinoma of the palate, a squamous cell carcinoma of the rumen, and a transitional cell carcinoma of the urinary bladder, repetitive DNA sequences present in the Ha-ras 1 locus showed anomalous restriction patterns, indicating rearrangements and, in the case of the palate cancer, amplification. Genomic DNA from several cancers was capable of inducing focus formation in the NIH3T3 transformation test. DNA from primary, secondary and tertiary transformants was analysed by hybridization to bovine ras probes and by nucleotide sequencing of polymerase chain reaction products. Bovine Ha-ras 1 sequences were found in all transformants, but no nucleotide differences were detected in exon 1 or exon 2 between normal, cancer and transformed cells. It is concluded that the Ha-ras 1 gene is activated in alimentary canal carcinomas, although the activating mutation has not yet been mapped. The possible relationship between papillomavirus infection and activation of the ras gene is considered.

Amino Acid Sequence↗
PubMed1987

The Leeuwenhoek lecture, 1986. Environmental carcinogens and papillomaviruses in the pathogenesis of cancer.

In many areas of the world there is a geographically localized high incidence of alimentary and bladder cancer in cattle. Studies in western Scotland have demonstrated that this phenomenon is associated with ingestion of bracken fern. However, the affected animals and herds were shown also to have an unusually high infection rate of alimentary papillomas caused by a previously unrecognised bovine papillomavirus (BPV) and that these tumors could undergo malignant transformation. Long-term field and experimental studies were started and indicate that the pathogenesis of the tumours and their relationship to virus infection and food-derived mutagens is complex. Results from these studies, and from cellular and molecular biology experiments, are presented and discussed in the context of recent papillomavirus findings in the human subject.

Animals↗