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

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.

1957 ◽  
Vol 106 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Wilbur Fiske Noyes ◽  
Robert C. Mellors

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.


1961 ◽  
Vol 114 (4) ◽  
pp. 485-500 ◽  
Author(s):  
Yohei Ito ◽  
Charles A. Evans

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.


1941 ◽  
Vol 73 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Thorolf Packalén

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.


1941 ◽  
Vol 74 (4) ◽  
pp. 321-344 ◽  
Author(s):  
John G. Kidd

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.


2010 ◽  
Vol 34 (8) ◽  
pp. S75-S75
Author(s):  
Weifeng Zhu ◽  
Zhuoqi Liu ◽  
Daya Luo ◽  
Xinyao Wu ◽  
Fusheng Wan

1977 ◽  
Vol 12 (1) ◽  
pp. 27-50 ◽  
Author(s):  
L.A. Behie ◽  
J.E. Zajic ◽  
D. Berk ◽  
R.J.P. Brouzes ◽  
V.A. Naish

Abstract Although Daphnia magna have been widely used in the determination of the toxicity of various substances, there are no reports in the literature that describe a rigorous bioassay method using this organism as a test species. The test described herein involves the standariza-tion of various important aspects of the method such as the age of the test organisms, and the dilution water used for the preparation of the various toxicant concentrations. Also described is a simple method for the statistical analysis of the results. The sensitivity of the proposed bioassay is demonstrated by determining the toxicity of various pulp and paper effluents. Finally, extensive bioassays were carried out simultaneously with rainbow trout and Daphnia magna indicating that Daphnia are as good a biological indicator of acute toxicity as fish.


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