Enhanced survival of ultraviolet-irradiated herpes simplex virus in human cytomegalovirus-infected cells.
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Animals↗
Biomedical subjects
F Rapp
Publications and source records attributed to F Rapp.
Quantification of plasminogen activator activity associated with herpesvirus-transformed cells.
Herpesvirus-transformed cell lines were examined for plasminogen activator (PA) activity using a quantitative assay. Previous results of cold fibrin overlay assays indicated that herpesvirus-transformed hamster cell lines produce fibrinolytic activity. Quantification of this activity involved the use of an 125I-fibrin lysis assay in which medium previously incubated with transformed or normal cells was tested for its ability to lyse 125I-fibrin polymers. This assay indicated an enhanced production of plasminogen-dependent fibrinolytic activity by transformed hamster cells compared to hamster embryo fibroblasts. The kinetics of secretion failed to reveal a significant difference in plasminogen activator activity in cells transformed by either herpes simplex virus types 1 or 2 (HSV-1 or HSV-2); however, transformed cells exhibited a significant increase in activity over non-transformed cells. Further characterization of PA activity associated with cells transformed by HSV-1 or HSV-2 has revealed that the protease is secreted and can function extracellularly. Extracellular PA activity produced by HSV-transformed cells is detected more efficiently than the cell-associated enzyme. Extracellular PA can be induced in two different species of cells by infection with partially inactivated HSV-2. Lytic infection of human embryo lung cells by HSV-2 strain 333 did not enhance activity, but infection of these cells with virus inactivated by u.v. irradiation resulted in increased PA levels from the cells. Increased enzyme levels were also detected in hamster embryo fibroblasts infected with partially inactivated virus. Further investigation of this enzyme function may determine whether increased levels of protease will indicate oncogenic transformation in vitro by herpesviruses.
Animals↗
Leukaemia reactivates mouse cytomegalovirus.
An established model for latency by mouse cytomegalovirus (MCMV) was used to assess the effects of leukaemia on reactivation of MCMV. After inoculation of 400 spleen focus-forming units of Friend leukaemia virus (FLV), a significant number of mice yielded MCMV in salivary glands and kidneys 4 to 5 weeks later. Administration of cyclophosphamide during FLV infection increased the percentage of MCMV-positive animals. These results suggest that cytomegalovirus infections in leukaemic patients may reactivate as a result of the leukaemia itself and may be exacerbated by chemotherapy.
Animals↗
Acute cytomegalovirus infections in leukemic mice.
Mice infected with 2 x 10(3) plaque-forming units of mouse cytomegalovirus (MCMV) 3 days after receiving 300 to 400 spleen focus-forming units of Friend leukemia virus developed a more severe MCMV infection than did normal animals. Increased severity was demonstrated by the increased amounts of MCMV recoverable from the salivary glands of leukemic mice 1 to 5 weeks postinfection. In addition, the difference in the number of virus isolations from the kidneys, spleens, livers, and lungs of animals (74 to 120) coinfected with MCMV and Friend leukemia virus compared with animals (49 of 120) infected with MCMV alone was significant (P less than 0.01). Both the 50% lethal dose and 50% infectious dose of MCMV in leukemic mice were lower than in normal animals. MCMV and Friend leukemia virus appear to interact by suppressing the ability of infected spleen cells to respond to mitogen-induced stimulation. The observations of increased severity of MCMV infections in leukemic mice closely parallel the situation observed in human leukemia patients who are at an increased risk of disease due to human cytomegalovirus infections. This mouse model may be useful in assessing the effect of antiviral (cytomegalovirus) therapy.
Animals↗
Identification of the herpes simplex virus DNA sequences present in six herpes simplex virus thymidine kinase-transformed mouse cell lines.
We have used a novel filter hybridization approach to detect and map the herpes simplex virus (HSV) DNA sequences which are present in four HSV thymidine kinase (HSVtk+)-transformed cell lines which were derived by exposure of thymidine kinase negative (tk-) mouse cells to UV light-irradiated HSV type 2 (HSV-2). In addition, we have mapped the HSV-1 DNA sequences which are present in two HSV-1tk+-transformed cell lines produced by transfection of tk- mouse cells with sheared HSV-1 DNA. The results of these studies can be summarized as follows. (i) The only HSV DNA sequences which were common to all HSVtk+-transformed cells were those located between map coordinates 0.28 and 0.32. Thus, this region contains all of the viral DNA sequences which are necessary for the expression of HSV-mediated tk transformation. (ii) Many of the cell lines also contained variable amounts of non-tk gene viral DNA sequences located between map coordinates 0.11 to 0.57 and 0.82 to 1.00, suggesting that incorporation of the viral DNA sequences located between these map coordinates is a relatively random event. (iii) The viral DNA sequences located between map coordinates 0 to 0.11 and 0.57 to 0.82 were uniformly absent from all of the HSVtk+ cell lines tested, suggesting that there is a strong negative selective pressure against incorporation of these viral DNA sequences.
Animals↗
Inhibition of herpes simplex virus type 2-induced biochemical transformation by interferon.
The effect of interferon on the biochemical transformation of thymidine kinase-deficient cells by UV-inactivated herpes simplex virus type 2 has been studied. Transformation was much less sensitive to the action of interferon than virus multiplication. However, the continuous presence of a high dose of interferon (2,000 U) inhibited transformation almost completely. Although we could not differentiate between the effect of interferon on fixation and expression of the virus thymidine kinase gene, data suggest that the inhibitory effect of interferon on transformation might be partially due to the suppression of virus thymidine kinase expression.
Animals↗
Biochemical transformation by temperature-sensitive mutants of herpes simplex virus type 1.
Biochemical transformation assays of herpes simplex virus type 1 temperature-sensitive (ts) mutants distinguished three groups of mutants with regard to their thymidine kinase (TK) transforming ability: those incapable of transferring the TK gene at either the permissive or restrictive temperatures (group I); those resembling the wild-type virus, and therefore able to transform at both the permissive and nonpermissive temperatures (group II); and those that failed to transform or exhibited very low transformation frequencies at the permissive temperature but were able to transform at the nonpermissive temperature (group III). Two mutants in group II exhibited greatly enhanced transformation efficiency at the permissive temperature. The ts lesions in the majority of the mutants tested map between 0.30 and 0.60 units on the viral genome. Mutants with TK-positive (TK+), but DNA-negative, phenotypes at the nonpermissive temperature produced no TK+ transformants at the permissive temperature and only unstable transformants at the nonpermissive temperature. This suggests that a function which is required for viral DNA synthesis is also required to obtain stable expression or to transfer the TK+ gene or both when transfer is mediated by the entire viral genome.
Cell Line↗
Acycloguanosine treatment of herpesvirus infections in footpads and nervous tissue of normal and immunosuppressed mice.
Treatment of herpes simplex virus type 1 (HSV-1)-infected mice with acycloguanosine resulted in significantly fewer virus isolates from nervous tissues than from tissues of untreated animals. Acycloguanosine also significantly reduced the mean titers of HSV-1 recovered from the footpads of drug-treated animals. The anti-herpetic activity of acycloguanosine was observed in both normal and immunosuppressed mice.
Acyclovir↗
Expression of type-common envelope antigens by herpes simplex virus type 2-transformed hamster cells.
At least ten polypeptides were detected on the surface of the herpes simplex virus type 1 (HSV-1) virion. Two of these polypeptides, having molecular weights of 30,000 and 33,000, were identified in two herpes simplex virus type 2-transformed cell lines (333-8-9 and 333-2-29) by immunoprecipitation and SDS-PAGE. The same two virion polypeptides previously were shown to be present in an HSV-1-transformed cell line (14-012-8-1, T-10). These observations suggest that genetic information coding for these polypeptides is in close proximity to that portion of the virus genome involved in transformation.
Animals↗
Herpesviruses and prostate carcinogenesis.
Prostatic cancer cell cultures possessed intracellular immunofluorescent antigens specific for human cytomegalovirus (CMV) but produced no infectious virus particles. Norman human prostatic tissue yielded a CMV isolate that transformed primary human embryo lung cells in vitro. These cell transformants were highly oncogenic when transplanted to athymic nude mice. Immunological studies revealed that sera from prostatic cancer patients reacted significantly more frequently with CMV-related antigens than sera from age-, race-, and socioeconomic status-matched benign prostate hyperplasia groups. Specific reactivity against CMV-transformed cells of lymphocytes from prostatic cancer patients was also detected. These complex findings indicate that CMV may be involved in the development of prostatic neoplasia.
Animals↗
Properties of mouse embryo fibroblasts transformed in vitro by infectious bovine rhinotracheitis virus.
Infection of CD-1 mouse embryo fibroblast(s) (MEF) with infectious bovine rhinotracheitis virus (IBRV) strain HMC resulted in persistent infection and subsequent transformation of these cells. IBRV-transformed MEF cultures consisted of short fibroblastoid cells, and IBRV-specific membrane and intracellular antigens were detectable in early in vitro passages by indirect imunofluorescence (IF) techniques. The presence of IBRV genetic information was confirmed in IF-positive and IF-negative cells by in situ hybridization. IBRV-transformed MEF induced fibrosarcomas in athymic nude mice given sc transplants. Infectious virus could not be rescued from the transformed cells or from tumor cells by cocultivation with rabbit kidney cells, by treatment with 5-iodo-2'-deoxyuridine, or by UV irradiation. Nontransformed control cells did not survive more than 10 in vitro passages and did not induce tumors when transplanted to athymic nude mice. These observations represent new data concerning the mouse cell-transforming potential of IBRV and confirm the presence of at least part of the virus genome in the transformants.
Animals↗
[Herpesvirus and human cancer].
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Burkitt Lymphoma↗
Herpesviruses and human cancer.
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Animals↗
Establishment and characterization of a new endometrial cancer cell line (SCRC-1).
A new human endometrial cell line, SCRC-1, has been established from a uterine adenocarcinoma. During a period of 57 weeks in culture, the SCRC-1 cells have been passaged over 100 times. Cultures have an epitheloid morphology, high mitotic activity, and a tendency to form multiple cell layers. The cells are polygonal and are arranged in pavement-like fashion. Most have multiple nucleoli, some are multinucleated, and all have heavily vacuolated cytoplasm. Pretreatment with iododeoxyuridine did not reveal viral markers by cocultivation or immunofluorescence techniques. Karyologic studies indicate that the SCRC11 cell line is essentially diploid with a small subpopulation of tetraploid cells. Over a period of 20 weeks, 1 of 14 athymic nude mice inoculated with SCRC-1 cells developed a tumor which histologically closely resembled the original human tumor. Cells were subsequently propagated from this tumor and the resulting epitheloid-like cell line was designated SCRC-1, Tu 1.
Adenocarcinoma↗
Trigeminal ganglion infection by thymidine kinase-negative mutants of herpes simplex virus.
The incidence of trigeminal ganglion infection after corneal inoculation of guinea pigs with thymidine kinase-negative mutants of herpes simplex virus was markedly reduced compared to infection after inoculation of thymidine kinase-positive virus. Thymidine kinase-negative herpes simplex virus replicated well in ocular tissues in which dividing or potentially dividing cells were present, but not in trigeminal ganglion infection of nondividing neurons. Thymidine kinase-positive virus, however, replicated well in ocular tissues as well as in trigeminal ganglion. These results suggest that thymidine kinase expression of herpes simplex virus may be important in infections of sensory ganglia.
Animals↗
Enhancement of host cell reactivation of ultraviolet-irradiated Herpes simplex virus by caffeine, hydroxyurea and 5-bromodeoxyuridine.
Enhancement of host cell reactivation (HCR) of ultraviolet (UV)-irradiated herpes simplex virus (HSV) was demonstrated in cell cultures pretreated with caffeine, hydroxyurea, or 5-bromodeoxyuridine (BrdUrd). The effect of caffeine on HCR was shown to depend on the time of drug treatment with respect to infection. In cultures treated with caffeine during the course of virus replication, the infectivity of irradiated HSV was reduced about nine-fold, while cultures pretreated with the drug before infection showed an increase in infectivity. The extent of HCR enhancement depended on the time interval between treatment with caffeine and infection, drug concentration, and the UV irradiation dose to which HSV was exposed. Magnitude of enhancement of HCR by caffeine differed in various cell species. The results suggest that enhanced HCR of UV-irradiated HSV by DNA antimetabolities is associated with DNA repair activated in consequence of cell DNA damage.
Animals↗