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Virchows Archiv : An International... 1994Virions resembling papovavirus were demonstrated in glial cells in the brain of an aged patient without overt progressive multifocal leukoencephalopathy. The patient was...
Virions resembling papovavirus were demonstrated in glial cells in the brain of an aged patient without overt progressive multifocal leukoencephalopathy. The patient was not in a severely immunocompromised state. On histological examination, only a few tiny incomplete necrotic foci were found in the subcortical area. These foci were widely dispersed. Rare, swollen oligodendroglial cells and astrocytes in which papovavirus capsid protein (VP-1) was demonstrated immunohistochemically were present around the foci. The two typical types of virus particles i.e. 35 to 40 nm round particles and elongated particles, were observed in the nuclei of the swollen glial cells. The latter were in the minority. Distinct crystals were also found in the nuclei. The centre-to-centre distance of the particles in the crystals, about 40 nm, and the electron-opaque spots of the round-shaped virions and of the elongated particles, were indicative of structural subunits of papovavirus capsids. This case provides further evidence that papovavirus, possibly JC virus, may be reactivated in the brains of aged patients who are not in an immunocompromised state.
Topics: Aged; Brain; DNA, Viral; Female; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal
PubMed: 8032537
DOI: 10.1007/BF00191445 -
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 Sep 1988BK virus (BKV) is a human papovavirus which latently infects a majority of the world population. Reactivation of this virus is associated with acute hemorrhagic...
BK virus (BKV) is a human papovavirus which latently infects a majority of the world population. Reactivation of this virus is associated with acute hemorrhagic cystitis, and BKV DNA has been found in human tumor tissue. BKV is one of many highly homologous papovaviruses, including simian virus 40 and JC virus, which display distinct host and cell-type specificities, transformation potentials, and pathologies. These differences are thought to be determined, in part, by the noncoding regulatory region of each virus, which contains the origin of replication and regulatory elements for both early and late gene expression. We have used linker scan mutants to map functional elements of a truncated BKV early promoter and enhancer and have studied the stereospecific requirements of these elements. We have also identified protein-binding regions through DNase protection studies. Our results show that a minimum of four elements are necessary for efficient early transcription, at least three of which correspond to DNase-protected domains. These protein-binding elements map to the TATA box and two nuclear factor 1 consensus sequences, one located within the enhancer repeat unit and the other located to the late side of the enhancer. The sequence of the fourth element is similar to the transcription factor Sp1 consensus sequence. Additional DNase-protected sites are centered over AP-1 and Sp1 consensus sequences. Finally, we find that the functional elements of the BKV early promoter and enhancer lack strict stereospecific requirements for efficient transcription.
Topics: BK Virus; Base Sequence; DNA, Viral; Enhancer Elements, Genetic; HeLa Cells; Humans; Molecular Sequence Data; Mutation; Plasmids; Polyomavirus; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Repetitive Sequences, Nucleic Acid; Transcription, Genetic
PubMed: 2841491
DOI: 10.1128/JVI.62.9.3378-3387.1988 -
Infection and Immunity Jul 1983The fatal outcome of K virus infection in infant mice and cytoxan-treated adult mice is related to their inability to mount a prompt antibody response to the virus....
The fatal outcome of K virus infection in infant mice and cytoxan-treated adult mice is related to their inability to mount a prompt antibody response to the virus. Athymic nude mice infected with K virus exhibited no clinical illness and no detectable virus-specific immunoglobulin G (IgG) response, but they did exhibit a low level of virus-specific immunoglobulin M response. Transfer of spleen cells from K virus-primed nude mice to infected infant mice conferred complete protection against K virus-induced mortality. This protection was diminished by the depletion of B cells but not by the depletion of adherent cells from the primed spleen cells. B cell response is therefore important in the recovery of nude mice from K virus infection.
Topics: Animals; Antibodies, Viral; B-Lymphocytes; Immunization, Passive; Immunoglobulin G; Immunoglobulin M; Macrophages; Mice; Mice, Inbred BALB C; Mice, Nude; Papillomaviridae; Polyomaviridae; Spleen; Tumor Virus Infections
PubMed: 6602771
DOI: 10.1128/iai.41.1.434-436.1983 -
Nucleic Acids Research Jan 1991Eukaryotic expression vectors have been used successfully in viral LT-expressing cell lines (ie. COS) to clone cDNAs encoding proteins that can be detected through their...
Eukaryotic expression vectors have been used successfully in viral LT-expressing cell lines (ie. COS) to clone cDNAs encoding proteins that can be detected through their bio-activity or reactivity with specific antibodies. Since Chinese hamster ovary cells (CHO) have been used extensively for the isolation and characterization of somatic cell mutants, we felt it would be an advantage to develop an expression cloning system in CHO cells. We have modified the eukaryotic expression vector CDM8 by replacing the polyoma and SV40 origins of replication with the 427bp non-coding region of the Syrian hamster papovavirus. Wild-type CHO cells and the CHO glycosylation-mutant Lec4A were transfected with plasmids bearing the early genes of either polyoma virus or hamster papovavirus in order to establish stable, LT antigen-expressing cell lines designated CHOP or CHOH, respectively. CHOP cell lines expressing polyoma LT antigen supported efficient replication of CDM8, but replicated pMH poorly. Conversely, CHOH cells expressing the hamster papovavirus LT antigen supported replication of pMH, and at a lower efficiency, CDM8. Replication of CDM8 and pMH vectors were equally efficient in selected CHOP and CHOH cell lines, respectively and comparable to that of CDM8 replication in COS-1 cells. A bacterial beta-galactosidase fusion gene inserted into the multiple cloning site of a CDM8 derivative was efficiently expressed when transiently transfected into CHOP and CHOH cells but not CHO cells since only the former supports autonomous plasmid replication. These results show that expression-cloning in CHO cells expressing either polyoma virus or hamster papovavirus LT antigens is possible using either the CDM8 or the pMH vectors, respectively.
Topics: Animals; Antigens, Polyomavirus Transforming; Cell Line; Cloning, Molecular; Cricetinae; DNA Replication; Female; Gene Expression; Genetic Vectors; Ovary; Plasmids; Transfection
PubMed: 2011514
DOI: 10.1093/nar/19.1.85 -
Journal of Medical Virology 1984Current techniques for the measurement of BK papovavirus (BKV) specific IgM include sucrose density gradient centrifugation followed by hemagglutination inhibition (HAI)...
Current techniques for the measurement of BK papovavirus (BKV) specific IgM include sucrose density gradient centrifugation followed by hemagglutination inhibition (HAI) or indirect immunofluorescent (IF) staining of BKV infected cells using a fluorescein conjugated anti-human IgM antibody. These techniques are cumbersome and labor intensive and do not lend themselves to testing large numbers of sera. A solid phase radioimmunoassay (RIA) was developed to facilitate the measurement of BKV IgG and IgM in large numbers of sera. Solid phase antigen was prepared by adsorbing CsCl purified BKV antigen to polyvinyl chloride microtiter plates. Following reaction with serum, bound immunoglobulin was detected with iodinated goat anti-human IgG or IgM. RIA for the measurement of BKV IgG was sensitive with titers approaching 10(-6). Determination of IgG titers by RIA and HAI showed good agreement (P less than 0.01, correlation coefficient = 0.74). Measurement of BKV IgM was not affected by the presence of BKV IgG as evidenced by sucrose density gradient fractionation of IgM positive sera, removal of IgG by treatment with S. aureus protein A, and addition of BKV IgG to BKV IgM. Rheumatoid factor (RF) gave false positive IgM titers in the presence of BKV IgG when RF titers were greater than or equal to 1:640 by latex agglutination testing and BKV IgG levels exceed 1:256 by HAI. False positives due to RF could be eliminated by treatment of sera with sheep anti-human IgG antisera. RIA for BKV IgM was specific as sera containing JCV-, cytomegalovirus (CMV)-, rubella-, or hepatitis B core antibody (anti HBc)-IgM were negative by RIA. RIA detected BKV IgM in several sera from renal dialysis or allograft patients with titers ranging from 1:400 to 1:128,000 and demonstrated that BKV IgM persisted in sera of renal allograft patients for as long as 343 days post transplantation.
Topics: Antibodies, Viral; BK Virus; Cross Reactions; Cytomegalovirus Infections; False Positive Reactions; Hepatitis B; Humans; Immunoglobulin G; Immunoglobulin M; JC Virus; Kidney Transplantation; Polyomavirus; Radioimmunoassay; Renal Dialysis; Rheumatoid Factor; Rubella; Time Factors
PubMed: 6092527
DOI: 10.1002/jmv.1890140204 -
Archives of Virology 1983
Topics: B-Lymphocytes; Erythrocytes; Humans; Lymphocytes; Microscopy, Electron; Papillomaviridae; Polyomaviridae; Receptors, Virus; Rosette Formation; T-Lymphocytes
PubMed: 6600921
DOI: 10.1007/BF01314133 -
Nucleic Acids Research Oct 1979Extensive physical mapping revealed that approximately 90% of the genomes of BKV(prototype, WT) and BKV (MM strain) are identical or closely related. Nucleotide... (Comparative Study)
Comparative Study
Extensive physical mapping revealed that approximately 90% of the genomes of BKV(prototype, WT) and BKV (MM strain) are identical or closely related. Nucleotide sequences of the non-homologous regions and a large portion of the homologous regions have been determined for both genomes. The coding sequence of small t antigen of BKV(MM) is 216 nucleotides shorter than that of BKV(WT), even though no differences in biological function of the t antigen was observed. Both genomes contain three similar sets of 44-61 base-pair repeated sequences. However, the DNA sequence of the tandem repeats is totally different between BKV (human cell as host) and SV40 (monkey cell as host). On the other hand, the region between the N-terminus of the T antigen genes and the origin of replication is dominated by a similar set of palindromic sequences in BKV and SV40 DNA. There is also extensive homology between the regions which code for proteins in BKV and SV40, suggesting a close evolutionary relationship.
Topics: Antigens, Viral; BK Virus; Base Composition; Base Sequence; DNA Restriction Enzymes; DNA, Viral; Genes, Viral; Papillomaviridae; Polyomaviridae; Polyomavirus; Protein Biosynthesis; Simian virus 40; Species Specificity; Transcription, Genetic
PubMed: 228246
DOI: 10.1093/nar/7.3.651 -
Laboratory Animal Science Jun 1987The role of hamster papovavirus as the etiology of transmissible lymphoma was investigated under strict conditions that prevented natural exposure to the lymphoma agent....
The role of hamster papovavirus as the etiology of transmissible lymphoma was investigated under strict conditions that prevented natural exposure to the lymphoma agent. In an initial experiment, 19 hamsters that were exposed naturally to transmissible lymphoma were placed in direct and indirect contact with weanling hamsters from an uninfected source. Lymphoma developed in the original infected hamsters as well as hamsters maintained in direct and indirect contact. In addition, one of the contact hamsters developed cutaneous epitheliomas, containing hamster papovavirus. Epithelioma homogenate was inoculated into primary hamster embryo cultures, in which hamster papovavirus replicated. Second and third passage tissue culture fluid containing hamster papovavirus induced lymphomas in suckling and weanling hamsters. Cell culture fluid from uninoculated embryo cultures was not oncogenic.
Topics: Animals; Cricetinae; Lymphoma; Mesocricetus; Papillomaviridae; Polyomaviridae; Tumor Virus Infections
PubMed: 3613507
DOI: No ID Found -
Journal of Virology Mar 1979After infection of permissive human fetal brain cells by BK human papovavirus (BKV), the vast majority of the cells were killed by the virus, but rare survivors were...
After infection of permissive human fetal brain cells by BK human papovavirus (BKV), the vast majority of the cells were killed by the virus, but rare survivors were recovered after frequent medium changes. These surviving cells grew and formed visible colonies after 5 to 6 weeks and were thereafter established as permanent cell lines. These cells, designated as BK-HFB cells, were persistently infected and shed BKV. Morphologically, they were small polygonal cells and had transformed growth properties. Their plating efficiency on solid substrates or in semisolid medium was high, and they were tumorigenic in athymic nude mice. Cloning experiments in medium containing BKV antiserum revealed that BKV did not persist in the cultures in a simple carrier state. All cloned cell lines were initially T-antigen negative and virus-free. However, every clone began to release BKV and again became persistently infected within 3 weeks after removal of BKV antiserum. After rigorous antibody treatment, four of seven clones still released virus spontaneously upon removal of antiserum; three clones have remained virus-free and are apparently cured. Although these cloned cell lines are T- and V-antigen negative when grown in antiserum-containing medium, they retain "free" or episomal BKV genomes; integrated viral DNA was not detected in any of the clones. These free genomes are indistinguishable from prototype BKV DNA and are found in much larger amounts in virus-shedding cell lines.
Topics: Antigens, Neoplasm; Antigens, Viral; BK Virus; Brain; Cell Line; Cell Transformation, Neoplastic; Cell Transformation, Viral; Clone Cells; DNA, Viral; Humans; Polyomavirus; Virus Replication
PubMed: 221672
DOI: 10.1128/JVI.29.3.1177-1185.1979