scholarly journals A STUDY OF QUANTITATIVE CHANGES OF THE SHOPE RABBIT PAPILLOMA VIRUS AT THE SITE OF INOCULATION IN THE SKIN OF THE COTTONTAIL AND DOMESTIC RABBIT

1941 ◽  
Vol 73 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Thorolf Packalén
Keyword(s):  
Papilloma Virus ◽  
Rabbit Skin ◽  
Active Virus ◽  
Cottontail Rabbit ◽  
Domestic Rabbit ◽  
Virus Content ◽  
Quantitative Changes ◽  
Short Time ◽  
Shope Papilloma Virus

By excising after varying intervals the site of inoculation of the rabbit skin injected intracutaneously with the Shope papilloma virus and titrating its virus content, it has been shown that demonstrable active virus disappears from the skin within approximately 24 hours. The disappearance of most of the virus within such a short time as 15 to 60 minutes makes a transportation of virus from the site of inoculation as a responsible factor unlikely. The rate of disappearance seems to be the same both in the domestic and in the cottontail rabbit.

scholarly journals FLUORESCENT ANTIBODY DETECTION OF THE ANTIGENS OF THE SHOPE PAPILLOMA VIRUS IN PAPILLOMAS OF THE WILD AND DOMESTIC RABBIT

1957 ◽  
Vol 106 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Wilbur Fiske Noyes ◽  
Robert C. Mellors
Keyword(s):  
Nucleic Acid ◽  
Early Stage ◽  
Fluorescent Antibody ◽  
Antibody Detection ◽  
Wild Rabbit ◽  
Papilloma Virus ◽  
Viral Antigens ◽  
Stage Of Development ◽  
Domestic Rabbit ◽  
Shope Papilloma Virus

The results obtained by a fluorescent antibody study of the Shope papilloma virus in papillomas of the wild and domestic rabbit are presented. In the wild rabbit papillomas the viral antigens occurred exclusively in the nucleus and were present in the differentiating cells of the keratohyaline layers and in the keratinized layers. The antigens were not present in the deeper proliferating epithelial cells of the papillomas. The Shope viral antigens were present in very minute amounts in papillomas of the domestic rabbit, as compared with papillomas of the wild rabbit, and were only detected in the superficial keratinized layers. It is postulated that virus is present in the nuclei of the proliferating cells of the papillomas of the wild and domestic rabbit but exists there in an early stage of development, consisting mainly of nucleic acid and deficient in protein, therefore non-antigenic and not demonstrable by fluorescent antibody. The nucleic acid moiety of the virus may be infective, and the protein component may provide immunologic specificity and serve to preserve transmissibility. The protein-deficient virus can be referred to as masked virus.

scholarly journals INDUCTION OF TUMORS IN DOMESTIC RABBITS WITH NUCLEIC ACID PREPARATIONS FROM PARTIALLY PURIFIED SHOPE PAPILLOMA VIRUS AND FROM EXTRACTS OF THE PAPILLOMAS OF DOMESTIC AND COTTONTAIL RABBITS

1961 ◽  
Vol 114 (4) ◽  
pp. 485-500 ◽  
Author(s):  
Yohei Ito ◽  
Charles A. Evans
Keyword(s):  
Deoxyribonucleic Acid ◽  
Virus Preparation ◽  
Minute Amount ◽  
Papilloma Virus ◽  
Domestic Rabbit ◽  
Intact Virus ◽  
Negative Findings ◽  
Domestic Rabbits ◽  
Tumorigenic Activity ◽  
Shope Papilloma Virus

A deoxyribonucleic acid preparation which showed infectivity and tumorigenic activity in domestic rabbits was isolated from the papillomatous tissue of wild cottontail rabbits by phenolic deproteinization procedure. The activity of the preparation could be completely abolished by its exposure to a minute amount (0.02 µg/ml) of DNAase. Antisera against Shope papilloma virus did not block the tumorigenic activity of the preparation, and trypsin and chymotrypsin had no effect on it. The extraction with phenol of a partially purified virus preparation also yielded extracts with tumorigenic potency. Extracts obtained from the domestic rabbit papilloma and submitted to phenolic deproteinization also proved infective and tumorigenic in rabbits of this sort, although the level of "tumorigenicity" was much lower than that of the cottontail preparations. Tests for intact virus, carried out with half of the extracts yielded wholly negative findings.

scholarly journals JOINT ACTION OF A CHEMICAL CARCINOGEN AND A NEOPLASTIC VIRUS TO INDUCE CANCER IN RABBITS

1951 ◽  
Vol 93 (5) ◽  
pp. 459-487 ◽  
Author(s):  
Stanfield Rogers ◽  
Peyton Rous
Keyword(s):  
Joint Action ◽  
Epidermal Cells ◽  
Malignant Change ◽  
Large Majority ◽  
Chemical Carcinogen ◽  
Chemical Carcinogens ◽  
Papilloma Virus ◽  
Rabbit Skin ◽  
Distinctive Morphology ◽  
Shope Papilloma Virus

Areas of rabbit skin previously rendered hyperplastic with turpentine were scarified, inoculated with the Shope papilloma virus, and covered with a dressing that contained 20-methylcholanthrene (MC) or 9:10-dimethyl-1:2-benzanthracene (9:10). The dressing was left on until healing had been well completed, a matter of 5 to 7 days. The papillomas which subsequently arose often appeared later, were fewer, and remained less vigorous than those due to the action of virus alone, but throughout several months they appeared to differ from these in no other ways. Then, more or less abruptly, the large majority became carcinomatous, frequently at several situations, whereas with few exceptions the control growths underwent no such alteration. The cancers were of the sorts ordinarily deriving, by secondary change, from epidermal cells infected with the virus. Collateral data have made plain that the hydrocarbons acted in their carcinogenic capacity to bring on the cancers. Indeed in control tests 9: 10 sometimes conferred latent neoplastic potentialities on uninoculated epidermis exposed to it while healing after scarification, a fact disclosed months later by painting these expanses with chloroform until hyperplasia occurred. Under the promoting influence of this agent papillomas formed which had the distinctive morphology of those induced by the chemical carcinogens. So strong and enduring were the effects of MC and 9:10 as to cause cancers to arise from many virus papillomas which were retrogressing after months of proliferation, that is to say under circumstances ordinarily unfavorable to malignant change. The facts justify the conclusion that the virus and the hydrocarbons acted jointly and in their carcinogenic capacities.

scholarly journals STUDIES OF THE MECHANISM OF ACTION OF THE SHOPE RABBIT PAPILLOMA VIRUS

1963 ◽  
Vol 117 (3) ◽  
pp. 521-542 ◽  
Author(s):  
Stanfield Rogers ◽  
Margaret Moore
Keyword(s):  
Mechanism Of Action ◽  
Synthetic Activity ◽  
Partial Specific Volume ◽  
Wild Rabbit ◽  
Simple Method ◽  
Physiochemical Properties ◽  
Papilloma Virus ◽  
Domestic Rabbit ◽  
Shope Papilloma Virus

These studies make plain that the Shope papilloma virus induces the production of an arginase in rabbit squamous epithelium, and provide evidence that the information for the synthesis of the enzyme is derived from the virus rather than the rabbit. This form of induction is therefore different from that brought about by chemicals such as galactosides (36). Striking differences were shown between the physiochemical properties of Shope virus-induced arginase and other arginases of domestic and Kansas cottontail rabbits. The absence of a requirement for manganese suggests the mechanism of splitting off urea from arginine by papilloma arginase probably differs from that of previously described arginases. These findings (particularly the experiments in which it was demonstrated that papilloma growth could be greatly reduced by giving animals supplemental arginine in the presence of small amounts of the arginase inhibitor, canavanine) provide evidence that suggests the following mechanism of action for the virus: viral DNA introduces into rabbit epithelium the information for the synthesis of an arginase for which the cells have no control mechanism. The arginase depletes cellular arginine and, in turn, the synthesis of arginine-rich nuclear histones (2), thereby freeing the nucleus for greater synthetic activity (4, 35), which results in more rapid growth of the papilloma cells. Domestic rabbit papillomas induced with purified virus derived from wild rabbit papillomas were shown to contain an antigen which reacts immunologically like a wild rabbit antigen. It was distinct from the arginase, the protein coat of the virus, and the Vx-2 antigen. The presence of the wild rabbit antigen seems indicative of integration of the virus DNA in the host genome of the wild rabbit. Other incidental findings include the description of a simple method, accurate to within 1 per cent, for determining the partial specific volume of a protein, and the description of a modification of the Richards and Schachman method (9) enabling the determination of the molecular weight and homogeneity of a protein with as little as 0.25 mg and with an accuracy of 2 per cent.

scholarly journals Cottontail Rabbit Papillomavirus (CRPV) Model System to Test Antiviral and Immunotherapeutic Strategies

2005 ◽  
Vol 16 (6) ◽  
pp. 355-362 ◽  
Author(s):  
Neil D Christensen
Keyword(s):  
Rabbit Model ◽  
Virus Infections ◽  
Papilloma Virus ◽  
Rabbit Skin ◽  
Clinical Model ◽  
Antiviral Therapies ◽  
Cottontail Rabbit ◽  
Virus Life Cycle ◽  
Mutant Strains

The cottontail rabbit papillomavirus (CRPV)/rabbit model has proven to be the most versatile pre-clinical model to test antiviral, immunopotentiating and immunotherapeutic strategies for papilloma-virus infections. We have utilized this model for many years and have recently observed significant improvements in the utility of the model. Improvements have included various techniques to infect rabbit skin sites with strains of wild-type and mutant CRPV DNA prepared using standard molecular biological procedures. A better understanding of the virus life cycle in vivo has been gained also from these studies such that we now have several defined strains of CRPV including i) antigenically diverse strains of CRPV, ii) mutant strains of CRPV with reduced growth rates, and iii) mutant strains of CRPV that demonstrate accelerated malignant progression rates. Collectively, these mutant genomes provide laboratories with a powerful pre-clinical model to assess a variety of antiviral therapies. Many of the treatments already tested in the CRPV/rabbit model have shown parallel efficacy against HPV infections in a clinical setting. Some of our recent experiences with the CRPV/rabbit model are outlined in this brief overview.

scholarly journals THE DETECTION OF A "MASKED" VIRUS (THE SHOPE PAPILLOMA VIRUS) BY MEANS OF IMMUNIZATION

1941 ◽  
Vol 74 (4) ◽  
pp. 321-344 ◽  
Author(s):  
John G. Kidd
Keyword(s):  
Induced Resistance ◽  
Passive Transfer ◽  
Papilloma Virus ◽  
Negative Results ◽  
Domestic Rabbit ◽  
Natural Hosts ◽  
Antiviral Antibody ◽  
Immunization Procedure ◽  
Decisive Evidence ◽  
Shope Papilloma Virus

A study has been made of the immunization procedure described by Shope, with particular reference to the detection of "masked" papilloma virus by means of it. Papilloma extracts were frequently encountered which, though non-pathogenic, elicited the specific antiviral antibody and induced resistance to the virus upon injection intraperitoneally into normal rabbits. The results of the immunization experiments were often complicated, however, by the effects of extravasated antibody, which had accumulated in various amounts in many of the papillomas and was consequently present in extracts of them together with "masked" virus. The extravasated antibody was often sufficient to render extracts of domestic rabbit papillomas non-antigenic; and sometimes, when present in excess, its passive transfer conferred resistance to reinfection with the virus. The conclusion seems warranted that only positive immunization findings can be interpreted with certainty. Negative results provide no decisive evidence as to whether "masked" virus is or is not present in the injected material, unless the amount of extravasated antibody also present is known. The findings may have a bearing on the negative outcome of immunization experiments with extracts of the cancers deriving from the natural papillomas of cottontails. Crude suspensions of domestic rabbit papillomas, which contain little or no virus demonstrable by ordinary methods, are far less antigenic than extracts of the natural growths of wild rabbits, which contain virus in quantity. In explanation of the finding the possibility seems worthy of attention that domestic rabbit papillomas may contain much less virus than the growths of cotton tails, the natural hosts of the virus.

scholarly journals EXPERIMENTS ON THE CAUSE OF THE RABBIT CARCINOMAS DERIVED FROM VIRUS-INDUCED PAPILLOMAS

1952 ◽  
Vol 96 (2) ◽  
pp. 159-174 ◽  
Author(s):  
Peyton Rous ◽  
John G. Kidd ◽  
William E. Smith
Keyword(s):  
Blood Stream ◽  
Papilloma Virus ◽  
Rate Of Growth ◽  
Vx2 Carcinoma ◽  
Domestic Rabbit ◽  
Negative Findings ◽  
Direct Inoculation ◽  
Epidermal Carcinoma

Tests were made to learn whether an anaplastic, epidermal carcinoma, the Vx2, which had originated more than 8 years previously from a virus papilloma in a domestic rabbit, still rendered its hosts immune to the virus. It had done so in the first 22 successive groups of animals to which it was transferred during a period of 3½ years, its growth regularly eliciting a blood antibody that neutralized the Shope virus and fixed complement in mixture with it; and on the assumption that this would continue to be the case no further observations were made for nearly 4½ years more. Then direct inoculation of animals carrying the tumor in its 46th Generation showed them to be as susceptible to the virus as normal rabbits; and sera procured from hosts of the 46th, 47th, 48th, and 50th Generations failed to neutralize the virus or fix complement with it. Tests of this last sort, repeated at intervals since,—most recently with sera from animals carrying the tumor in its 73rd Generation,—have yielded consistently negative findings. Loss of the power to immunize against the papilloma virus was not attended by any perceptible change in the Vx2 carcinoma. Manifestly the antigen responsible for the immunity cannot, as such, have been the actuating cause of the tumor. Attempts were made to infect the cells providing 48th Generation cancers, by mixing them with a suspension of the papilloma virus at time of implantation, or by injecting this agent into the blood stream of rabbits in which the tumog had already begun to proliferate. Its morphology and rate of growth remained unaltered; but tests of the animals to which transfers were next made yielded what appeared to be evidence of some slight immunity to the virus.

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