Oncogenic properties of human viruses.
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Biomedical subjects
Publications and source records attributed to F Rapp.
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Using a direct immunofluorescence technique, herpes simplex virus type 1 (HSV-1)-transformed cells and cell lines subsequently derived from tumors and metastases were examined for the presence of HSV-1-associated surface antigens. Fluorescein-labeled immunoglobulins derived from antisera were used and included anti-HSV-1 (from hamsters), sera from tumor-bearing hamsters, and antibodies prepared in rabbits against cell material shed early into the medium after infection of rabbit kidney cells with HSV-1. All immunoglobulins showed the greatest reactivity with cell lines derived from tumors and metastatic lesions. There appeared to be little or no reactivity on the surfaces of the transformed cells. Transformed cells treated with 5-iodo-2'-deoxyuridine for 48 h, however, showed an enhanced reactivity which approached that seen with the tumor-derived cell lines.
Transformation potential of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was quantitatively compared in a system selecting for biochemical transformants. The highest frequency of transformation was obtained with HSV-2 strain 333. The transformation rates for two strains of HSV-1 were lower and distinctly different from HSV-2 and from each other. The dose of inactivating ultraviolet light received by the virus and the multiplicity of infection proved to be critical components of the procedure. Clones of these biochemically transformed cells expressed HSV-specific antigens, altered cell morphology, and increased levels of thymidine kinase activity. Isolates of HSV-1 recovered from the same site 11 years apart yielded similar transforming frequencies. These results suggest that this assay should prove useful in further characterizing the biological properties of HSV.
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Human viruses known to be spread by sexual contact include herpes simplex viruses (HSV), papillomaviruses (HPV), human immunodeficiency virus (HIV), hepatitis B virus, and cytomegalovirus. Infections with the first three (HSV, HPV, and HIV) have reached epidemic proportions and pose global health concerns. Most of what we know about these human pathogens has been learned only recently, owing to the advent of DNA technologies and advances in culture techniques. In fact, our awareness of one virally transmitted venereal disease, acquired immunodeficiency syndrome, dates to the early 1980s. This paper touches on various aspects of the biology, pathogenesis, clinical manifestations, and, where applicable, oncogenicity of these agents, as well as current treatments and vaccine initiatives.
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Urogenital tissue specimens were maintained in culture for 2 years. Epithelioid growth was enhanced with use of collagenase digestion rather than trypsinization. Twenty of 34 prostate cancer cell cultures survived more than ten in vitro passages, during which time four of 20 demonstrated epithelioid morphology. One epithelioid line (T-157) survived 32 in vitro passages. The cells demonstrated lack of contact inhibition in culture, were slightly positive in acid phosphatase tests, and reacted positively with cytomegalovirus (CMV)-immune sera in indirect immunofluorescence (IF) tests. These cells, which were proven to be of human male origin, failed to yield infectious virus and could be re-isolated from a nodule induced by the cells when injected sc into weanling athymic nude mice. The serum of the patient from which the tumor cells were derived demonstrated high CMV antibody titers and reacted with the virus-specific membrane and intracellular antigens of CMV-transformed human cells in IF tests. A CMV strain isolated from one of the normal prostate cell cultures established an in vitro long-term persistent infection of human embryo lung cells which resulted in the development of two transformed cell lines. The transformed cells possessed CMV antigenic markers and induced non-differentiated tumors when transplanted into athymic nude mice. The results constitute further evidence of the transforming capacity of CMV, and suggest that the virus may be oncogenic in its natural (human) host.