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Conserved polynucleotide sequences among the genomes of papillomaviruses.

The DNAs of different members of the Papillomavirus genus of papovaviruses were analyzed for nucleotide sequence homology. Under standard hybridization conditions (Tm - 28 degrees C), no homology was detectable among the genomes of human papillomavirus type 1 (HPV-1), bovine papillomavirus type 2 (BPV-2), or cottontail rabbit (Shope) papillomavirus (CRPV). However, under less stringent conditions (i.e., Tm - 43 degrees C), stable hybrids were formed between radiolabeled DNAs of CRPV, BPV-1, or BPV-2 and the HindIII-HpaI A, B, and C fragments of HPV-1. Under these same conditions, radiolabeled CRPV and HPV-1 DNAs formed stable hybrids with HincII B and C fragments of BPV-2 DNA. These results indicate that there are regions of homology with as much as 70% base match among all these papillomavirus genomes. Furthermore, unlabeled HPV-1 DNA competitively inhibited the specific hybridization of radiolabeled CRPV DNA to bpv-2 DNA fragments, indicating that the homologous DNA segments are common among these remotely related papillomavirus genomes. These conserved sequences are specific for the Papillomavirus genus of papovaviruses as evidenced by the lack of hybridization between HPV-1 DNA and either simian virus 40 or human papovavirus BK DNA under identical conditions. These results indicate a close evolutionary relationship among the papillomaviruses and further establish the papillomaviruses and polyoma viruses as distinct genera.

Base Sequence

Multiple copies of Shope virus DNA are present in cells of benign and malignant non-virus-producing neoplasms.

In an initial efforts to characterize the virological basis of neoplasia in the Shope papilloma-carcinoma system, the extent to which the viral genome is present in non-virus-producing benign and malignant tumors in domestic rabbits was established. Employing nick-translated radioactive viral DNA purified from productively infected papillomas on cotton tail rabbits as a probe, it was found that (i) papillomas, primary carcinomas, and metastatic carcinomas contain 10 to about 100 copies of the viral genome per diploid cell equivalent of DNA and (ii) viral DNA is present in detectable amounts in essentially all neoplastic cells. These results are consistent with the suggestion that continued presence of the viral genome is necessary for induction and maintenance of malignant as well as benign neoplasms.

Animals

[Interactions of Shope papilloma virus with SV40 in adult domestic rabbit cell lines derived from normal skin or from Shope papilloma virus infected skin (author's transl)].

Three cell lines from adult domestic rabbit are infected with SV40: LP 17 and LP 45 derived from normal skin and LP 42 PS derived from skin infected for 24 h with Shope papilloma virus. The fibroblastic morphology of the cultures is not changed. SV40 is not recovered and T antigen is only detected in LP 42 PS cell line after 29 passages. To know if Shope papilloma virus facilitates penetration of SV40, cultures of LP 45 are first infected with Shope papilloma virus for 2 h and for 24 h, then superinfected with SV40. There is no cellular alteration, and T antigen induced by SV40 is only detected in cells pretreated for 24 h with Shope papilloma virus, after 20 passages. When cultures LP 45 are infected with Shope papilloma virus neutralized with a high titer antiserum and superinfected with SV40, T antigen is not detected. Superinfected cells containing specific SV40 T antigen do not induce tumors either in new born hamsters or in rabbits but they are able to grow in colonies in soft agar. LP 42 PS cell line and LP 45 cells infected with Shope papilloma virus for 24 h containe Shope papilloma virus genome which is able to modify the permissivity of rabbit cells to SV40.

Animals

Spontaneous tumor regression: possible relationship to in vitro parameters of tumor immunity.

Evidence is discussed from three animal systems (Shope papillomas in rabbits, Moloney sarcomas in mice, Schmidt-Ruppin-Rous sarcomas in Japanese quail) that immune reactions can be important in spontaneous tumor regression. In vitro studies performed in these systems indicate that blocking serum factors can thwart cell-mediated immune responses and that "unblocking" antibodies are often found in animals whose tumors have regressed. To what extent spontaneous regressions of human neoplasms are due to immunologic mechanisms is unknown; in 2 patients who had undergone spontaneous tumor regression, tumor cell cytotoxic lymphocytes and unblocking serum factors were detected. Better animal models and better knowledge about the mechanisms of tumor immune reactions are needed before tumor regression can be more successfully induced by immunologic manipulation (to what extent that will even be feasible in man is unknown).

Animals

Interactions of Shope papilloma virus with some other DNA viruses.

The interactions of Shope papilloma virus (SPV) with primate and rabbit cells in tissue culture have been investigated. The rabbit cell cultures were derived from normal epidermis, from SPV-infected epidermis, from SPV-induced papillomas, and from an SPV-associated carcinoma. None of these cell cultures, whether infected in vitro with SPV or derived from tissues infected in vivo, ever produced infectious SPV or even detectable viral antigens. Some other DNA viruses behaved differently in cells which had been in previous contact with SPV either in vitro or in vivo. Adenovirus type 5 multiplies better in human cells infected 24 h previously with SPV than in the untreated controls. The production of infectious virions of either herpes simplex virus or Shope fibroma virus is reduced in cells derived from SPV-induced papillomas or carcinoma, due, apparently, to a defect in viral maturation. Of the rabbit cells, only those derived from in vivo infected tissue, or those previously infected in vitro with SPV, could be transformed by SV40. The rabbit cell lines derived from papillomas or carcinoma differed from their counterparts derived either from normal epidermis or from tissue infected 24 hrs before biopsy, in their karyotype, and in their ability to grow in soft agar. Similar karyotypic alterations were induced in cells derived from healthy epidermis by infection in vitro with SPV.

Adenoviruses, Human