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Journal of Bacteriology Feb 1966Feldman, Lawrence A. (Baylor University College of Medicine, Houston, Tex.), Janet S. Butel, and Fred Rapp. Interaction of a simian papovavirus and adenoviruses. I....
Feldman, Lawrence A. (Baylor University College of Medicine, Houston, Tex.), Janet S. Butel, and Fred Rapp. Interaction of a simian papovavirus and adenoviruses. I. Induction of adenovirus tumor antigen during abortive infection of simian cells. J. Bacteriol. 91:813-818. 1966.-Adenovirus types 2, 7, and 12 undergo an abortive growth cycle in green monkey kidney cells; they induce the formation of adenovirus tumor antigen, but synthesis of adeno capsid antigen and infectious adenovirus was observed only when cultures were concomitantly infected with a simian papovavirus (SV40). Several other viruses, including herpes simplex and measles which replicate in monkey cells, and rabbit papilloma and human wart papovaviruses which do not, failed to stimulate adenovirus replication in the monkey cells. Adenovirus tumor antigen was detected 8 to 10 hr postinfection by immunofluorescent techniques. The antigen induced by adenovirus types 2 and 7 appeared as intranuclear masses; adenovirus type 12 tumor antigen also appeared as cytoplasmic and nuclear flecks. Sera from hamsters bearing tumors induced by adenovirus type 12 cross-reacted with tumor antigens induced by types 2 and 7 but not with antigens induced by SV40.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Antigens; Haplorhini; In Vitro Techniques; Measles virus; Microscopy, Fluorescence; Oncogenic Viruses; Papillomaviridae; Polyomaviridae; Simian virus 40; Simplexvirus; Virus Cultivation
PubMed: 4286827
DOI: 10.1128/jb.91.2.813-818.1966 -
Journal of Virology Apr 1979JC human papovavirus was found to replicate in primary human amnion cells. The virus has undergone eight passages in amnion cells and was identified by serological...
JC human papovavirus was found to replicate in primary human amnion cells. The virus has undergone eight passages in amnion cells and was identified by serological methods as JC virus. By restriction endonuclease analysis of the viral DNA, the fragments observed were identical to those previously reported for the prototype strain.
Topics: Amnion; Antigens, Viral; Culture Techniques; Cytopathogenic Effect, Viral; DNA, Viral; Humans; Leukoencephalopathy, Progressive Multifocal; Molecular Weight; Papillomaviridae; Polyomaviridae; Virus Replication
PubMed: 480459
DOI: 10.1128/JVI.30.1.384-389.1979 -
Frontiers in Immunology 2019Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection with JC-virus (JCV), a papova-virus, affecting mostly oligodendrocytes and the white...
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection with JC-virus (JCV), a papova-virus, affecting mostly oligodendrocytes and the white matter of the central nervous system. Progressive Multifocal Leukoencephalopathy (PML) almost exclusively occurs in immunocompromised patients based on different underlying conditions of severe cellular immunodeficiency such as HIV/AIDS, secondary to neoplastic and autoimmune diseases, or during immunosuppressive therapy. We present the case of an otherwise healthy and immunocompetent patient without immunosuppressive therapy who was admitted with hemianopsia to the right side, sensory aphasia and changes of behavior. Magnet resonance imaging (MRI) and laboratory testing confirmed the diagnosis of PML, although functional tests did not show any evidence for cellular immunodeficiency. Extensive immunological tests did not reveal an apparent immunodeficiency. During symptomatic therapy the patient developed seizures which were assumed to be caused by a spontaneous immune reconstitution inflammatory syndrome (IRIS) demonstrated by MRI. We added a high dose of intravenous corticosteroids to the antiepileptic treatment and seizures ended shortly thereafter. However, the impairments of vision, behavior and language persisted. Our case report highlights that an apparently immunocompetent patient can develop PML and IRIS spontaneously. Therefore, MRI should be applied immediately whenever a rapid progression of PML symptoms occurs as treatment of IRIS with corticosteroids can result in a marked clinical improvement.
Topics: Aged; Brain; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; JC Virus; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Positron-Emission Tomography; Serologic Tests
PubMed: 31191548
DOI: 10.3389/fimmu.2019.01188 -
Transgenic Research Feb 2012For many CNS acting drugs, penetration into the central nervous system (CNS) is limited by the blood-CNS-barriers. In an effort to quantitate the role of the protein...
For many CNS acting drugs, penetration into the central nervous system (CNS) is limited by the blood-CNS-barriers. In an effort to quantitate the role of the protein components that make up the blood-CNS-barriers, we created transgenic mice that allow conditional gene knockout using Cre/loxP technology. We targeted the expression of Cre-recombinase to the choroid plexus (the blood-cerebral spinal fluid barrier) using the lymphotropic papovavirus control region (LPVcr) and to brain endothelium (the blood-brain-barrier) using the proximal promoter region of the human von Willebrand Factor gene (hVWF-f). We verified that LPVcr restricts expression to the choroid plexus in adult mice by using the LPVcr to drive n-LacZ expression in transgenic mice. The LPV-Cre and hVWF-Cre plasmids were then constructed and tested for Cre-recombinase function in vitro, and subsequently used to create transgenic mice. The resulting transgenic mice were characterized for cell-type specific Cre-mediated endonuclease activity by crossing them with transgenic mice containing a loxP-flanked-LacZ/EGFP dual reporter gene Z/EG. The dual Cre-Z/EG transgenic offspring were evaluated for the location of EGFP mRNA expression by reverse transcriptase PCR and for protein expression by immunohistochemistry. Immunohistochemistry for EGFP verified expression in the target cells, and no ectopic expression outside of the expected cell types. The LPV-Cre.0607 transgenic line expressed functional Cre only in the choroid plexus and hVWF-Cre.1304 line in brain endothelium.
Topics: Animals; Blood-Brain Barrier; Cerebrospinal Fluid; Choroid Plexus; Gene Knockout Techniques; Green Fluorescent Proteins; Humans; Integrases; Lac Operon; Mice; Mice, Inbred C57BL; Mice, Transgenic; Organ Specificity; Promoter Regions, Genetic; von Willebrand Factor
PubMed: 21538071
DOI: 10.1007/s11248-011-9512-z -
Blood Aug 1989Adenosine deaminase (ADA) deficiency is associated with a fatal severe combined immunodeficiency. Because most patients do not have a suitable marrow donor, the...
Adenosine deaminase (ADA) deficiency is associated with a fatal severe combined immunodeficiency. Because most patients do not have a suitable marrow donor, the introduction of a normal ADA gene into the patient's marrow cells is a potentially useful alternative therapy. To identify vectors that provide optimal gene expression in human hematopoietic cells, we investigated retroviral vectors containing the ADA gene under the transcriptional control of the promoter/enhancers of Moloney murine leukemia virus, the simian virus 40 early region, the cytomegalovirus immediate-early gene, the lymphotropic papovavirus, and the human beta-globin gene. ADA expression from these vectors was monitored in the ADA- human histiocytic lymphoma cell line DHL-9, and in the multipotential chronic myeloid leukemia cell line K562. ADA expression in infected K562 cells was also measured after induction of megakaryoblastic differentiation by phorbol ester, and after induction of erythroid differentiation by sodium n-butyrate or hemin. In these hematopoietic cell lines, the vectors that contained ADA controlled by either the Moloney murine leukemia virus promoter (LASN) or the cytomegalovirus promoter (LNCA) expressed ADA at much higher levels than the other vectors tested. Furthermore, in K562 cells infected with LASN and LNCA vectors, induction of terminal differentiation resulted in the same or higher level expression of ADA. These cell lines have permitted the evaluation of transduced gene expression in proliferating and differentiating hematopoietic cells that provide a model for bone marrow-targeted gene therapy.
Topics: Adenosine Deaminase; Animals; Cell Line; Cloning, Molecular; Genes; Genetic Vectors; Hematopoietic Stem Cells; Humans; Leukemia, Erythroblastic, Acute; Lymphoma; Mice; Nucleoside Deaminases; Promoter Regions, Genetic; Transfection; Tumor Cells, Cultured
PubMed: 2752148
DOI: No ID Found -
Journal of Virology Dec 1989Replication of papovavirus DNA requires a functional replication origin, a virus-encoded protein, large T antigen, and species-specific permissive factors. How these... (Comparative Study)
Comparative Study
Replication of papovavirus DNA requires a functional replication origin, a virus-encoded protein, large T antigen, and species-specific permissive factors. How these components interact to initiate and sustain viral DNA replication is not known. Toward that end, we have attempted to identify the viral target(s) of permissive factors. The functionally defined replication origins of polyomavirus and simian virus 40, two papovaviruses that replicate in different species (mice and monkeys, respectively), are composed of two functionally distinct domains: a core domain and an auxiliary domain. The origin cores of the two viruses are remarkably similar in primary structure and have common binding sites for large T antigen. By contrast, their auxiliary domains share few sequences and serve as binding sites for cellular proteins. It seemed plausible, therefore, that if cellular permissive factors interacted with the replication origin, their targets were likely to be in the auxiliary domain. To test this hypothesis we constructed hybrid origins for DNA replication that were composed of the auxiliary domain of one virus and the origin core of the other and assessed their capacity to replicate in a number of mouse and monkey cell lines, which express the large T antigen of one or the other virus. The results of this analysis showed that the auxiliary domains of the viral replication origins could substitute for one another in DNA replication, provided that the viral origin core and its cognate large T antigen were present in a permissive cellular milieu. Surprisingly, the large T antigens of the viruses could not substitute for one another, regardless of the species of origin of the host cell, even though the two large T antigens bind to the same sequence motif in vitro. These results suggest that species-specific permissive factors do not interact with the origin-auxiliary domains but, rather, with either the origin core or the large T antigen or with both components to effect DNA replication.
Topics: Animals; Antigens, Polyomavirus Transforming; Base Sequence; Cell Line; Cells, Cultured; Cloning, Molecular; DNA Replication; Molecular Sequence Data; Papillomaviridae; Plasmids; Polyomaviridae; Polyomavirus; Restriction Mapping; Sequence Homology, Nucleic Acid; Simian virus 40
PubMed: 2555562
DOI: 10.1128/JVI.63.12.5371-5385.1989 -
Journal of Virology Aug 1984Papovavirus K (K virus) is a murine papovavirus that produces a fatal interstitial pneumonia in newborn mice and a clinically inapparent infection in older animals. The...
Papovavirus K (K virus) is a murine papovavirus that produces a fatal interstitial pneumonia in newborn mice and a clinically inapparent infection in older animals. The present study was conducted to determine whether the virus produces latent infection in animals surviving acute infection and whether the infection can be reactivated by immunosuppression. Mice were inoculated by the oral route with 100 newborn mouse 50% lethal doses at 12 days of age and followed for 8 months by using immunofluorescence staining. Cells positive for K virus capsid antigen were found in lungs, livers, kidneys, intestines, and brains for 6 months, but not thereafter. Organ examined at 8 months were negative for virus by tissue culture assay, mouse inoculation, explantation, and cocultivation. Immunosuppression of the remaining animals with 8 weekly injections of cyclophosphamide (150 mg/kg) resulted in the reappearance of viral antigen and infectious virus in multiple organs including brains. The highest titers of virus were present in kidneys. One animal sacrificed after 42 days of immunosuppression was found to have a small pulmonary adenoma or alveologenic carcinoma, but efforts to explant this tumor into tissue culture were unsuccessful. The present study demonstrates that K virus produces a latent infection that is reactivated by immunosuppression, and our results raise questions as to whether reactivated infection may occasionally be associated with the development of neoplasia.
Topics: Animals; Brain; Fluorescent Antibody Technique; Hemagglutination Inhibition Tests; Hemagglutination Tests; Immune Sera; Immunosuppression Therapy; Intestines; Kidney; Liver; Lung; Lung Neoplasms; Mice; Organ Specificity; Papillomaviridae; Polyomaviridae; Spleen; Tumor Virus Infections
PubMed: 6379207
DOI: 10.1128/JVI.51.2.425-429.1984 -
Journal of Virology Aug 1994Small DNA viruses are dependent on the interaction of early proteins (such as large T antigen) with host p53 and Rb to bring about the G1-to-S cell cycle transition. The...
Small DNA viruses are dependent on the interaction of early proteins (such as large T antigen) with host p53 and Rb to bring about the G1-to-S cell cycle transition. The large DNA viruses are less dependent on host regulatory genes since additional early viral proteins (such as viral DNA polymerase, DNA metabolic enzymes, and other replication proteins) are involved in DNA synthesis. A highly conserved domain of large T antigen (similar to the p53-binding region) exclusively identifies papovavirus, parvovirus, and papillomaviruses from all other larger DNA viruses and implies a conserved interaction with host regulatory genes. In this report, we show that 3 to 6 mM butyrate, a general cell cycle blocker implicated in inhibition of the G1-to-S transition, inhibits DNA replication of polyomavirus and human papillomavirus type 11 but not the replication of larger DNA viruses such as adenovirus types 2 and 5, herpes simplex virus type 1, Epstein-Barr virus, and cytomegalovirus, which all bypass the butyrate-mediated cell cycle block. This butyrate effect on polyomavirus replication is not cell type specific, nor does it depend on the p53 or Rb gene, as inhibition was seen in fibroblasts with intact or homozygous deleted p53 or Rb, 3T6 cells, keratinocytes, C2C12 myoblasts, and 3T3-L1 adipocytes. In addition, butyrate did not inhibit expression of polyomavirus T antigen. The antiviral effect of butyrate involves a form of imprinted state, since pretreatment of cells with 3 mM butyrate inhibits human papillomavirus type 11 DNA replication for at least 96 h after its removal. Butyrate, therefore, serves as a molecular tool in dissecting the life cycle of smaller DNA viruses from that of the larger DNA viruses in relation to the cell cycle.
Topics: Adenoviridae; Animals; Butyrates; Butyric Acid; Cell Cycle; Cell Line; HeLa Cells; Herpesviridae; Humans; Mice; Papillomaviridae; Polyomavirus; Virus Replication
PubMed: 8035479
DOI: 10.1128/JVI.68.8.4785-4796.1994 -
Journal of Virology Nov 1982The origin of adenovirus DNA replication lies within an inverted sequence repetition at either end of the linear, double-stranded viral DNA. Initiation of DNA...
The origin of adenovirus DNA replication lies within an inverted sequence repetition at either end of the linear, double-stranded viral DNA. Initiation of DNA replication is primed by a deoxynucleoside that is covalently linked to a protein, which remains bound to the newly synthesized DNA. We demonstrate that virion-derived DNA-protein complexes from five human adenovirus serological subgroups (A to E) can act as a template for both the initiation and the elongation of DNA replication in vitro, using nuclear extracts from adenovirus type 2 (Ad2)-infected HeLa cells. The heterologous template DNA-protein complexes were not as active as the homologous Ad2 DNA, most probably due to inefficient initiation by Ad2 replication factors. In an attempt to identify common features which may permit this replication, we have also sequenced the inverted terminal repeated DNA from human adenovirus serotypes Ad4 (group E), Ad9 and Ad10 (group D), and Ad31 (group A), and we have compared these to previously determined sequences from Ad2 and Ad5 (group C), Ad7 (group B), and Ad12 and Ad18 (group A) DNA. In all cases, the sequence around the origin of DNA replication can be divided into two structural domains: a proximal A . T-rich region which is partially conserved among these serotypes, and a distal G . C-rich region which is less well conserved. The G . C-rich region contains sequences similar to sequences present in papovavirus replication origins. The two domains may reflect a dual mechanism for initiation of DNA replication: adenovirus-specific protein priming of replication, and subsequent utilization of this primer by host replication factors for completion of DNA synthesis.
Topics: Adenoviruses, Human; Base Composition; DNA Replication; DNA, Viral; Repetitive Sequences, Nucleic Acid; Templates, Genetic; Virus Replication
PubMed: 7143575
DOI: 10.1128/JVI.44.2.530-537.1982 -
Journal of Virology Mar 1974JC virus was found to have a buoyant density of 1.20 g/cm(3) in linear sucrose-D(2)O and 1.35 g/cm(3) in cesium chloride isopycnic gradients. DNA extracted either from... (Comparative Study)
Comparative Study
JC virus was found to have a buoyant density of 1.20 g/cm(3) in linear sucrose-D(2)O and 1.35 g/cm(3) in cesium chloride isopycnic gradients. DNA extracted either from JC-infected cultures or from gradient-purified virions occupied a dense position relative to linear DNA in cesium chloride/ethidium bromide gradients, and the circular configuration of the extracted DNA was confirmed by electron microscopy, with a measured molecular weight of 2.93 x 10(6). DNA from BK virus was similarly prepared and compared to JC and to an SV40 DNA standard by digestion with restriction endonuclease preparations from Haemophilus influenzae, Haemophilus parainfluenzae, and Escherichia coli. Digests were electrophoretically analyzed on gradient polyacrylamide slab gels or agarose gels, and the three viruses were found to have distinctly different cleavage patterns by this form of analysis: JC and BK viruses were almost entirely different from SV40 and significantly different from each other. Thus, JC and BK human papovaviruses appear to be discrete new members of the papovavirus group, rather than SV40 variants.
Topics: Centrifugation, Density Gradient; DNA, Circular; DNA, Viral; Electrophoresis, Polyacrylamide Gel; Endonucleases; Escherichia coli; Haemophilus; Haemophilus influenzae; Microscopy, Electron; Molecular Weight; Papillomaviridae; Polyomaviridae; Polyomavirus; Simian virus 40; Thymidine; Tritium
PubMed: 4362864
DOI: 10.1128/JVI.13.3.614-622.1974