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viruses harboured in blasts of the rat myelogenous leukemia (rba-le), induced by chicken sarcoma virus.it was shown that the rat myelogenous leukemia rba-le harbours three kinds of viruses. 1. rat leukemogenic virus, which can be recovered from leukemic cells, medium of cultured leukemic cells and the plasma of leukemic rats. about 12% of rats inoculated when newborn with the recovered virus developed leukemia. 2. chicken sarcoma virus, which seems to have a lowered infectivity or altered host range as the b77(rbi) virus by which this leukemia had been induced. 3. a cytopathic, hemagglutinating v ...1975175303
isolation and structural characterization of monomeric and dimeric forms of replicative intermediates of kilham rat virus dna.two virus-specific species of newly synthesized dna were isolated from rat fibroblast cell cultures infected with the kilham rat virus (rv). these two dna species were purified; their behavior on hydroxyapatite chromatography and their sedimentation coefficients in sucrose gradients were determined. one of the two species corresponds to the linear double-stranded form of the rv dna, and the other corresponds to the dimeric duplex form. after denaturation, a fraction of both species showed an int ...1976185420
persistent infection of a human lymphocyte cell line (molt-4) with the kilham rat virus.inoculation of a human thymus-derived lymphocyte cell line (molt-4) with the kilham rat virus resulted in persistently infected cultures, that released infectious virus for periods up to seven months. at any time following infection, a small percentage of the cells were positive for rat virus antigens as determined by immunofluorescene assay.1978203637
studies on the replication of krv single-stranded linear dna.the autonomous parvovirus, kilham rat virus (krv), is composed of three structural proteins (salzman & white, 1970) and a single molecule of dna. the dna molecule is linear and single-stranded (ss). it is believed to have both 3' and 5'-terminal palindromic sequences (salzman, 1977). replication of the ss dna may involve double-stranded (ds) dna intermediates of one unit length as found in the virion or multiple length concatamers (salzman & white, 1973; gunther & may, 1976; lavelle & li, 1977). ...1978207822
in vitro synthesis of double-stranded dna from the kilham rat virus single-stranded dna genome.double-stranded, full-length linear dna was synthesized in vitro by using single-stranded linear dna as a self-priming template from the parvovirus kilham rat virus and escherichia coli dna polymerase "large fragment" as the polymerizing enzyme. to ascertain the order of the synthesis of the cleavage fragments and to assess the accuracy of the in vitro synthesis, restriction endonuclease cleavage sites with known recognition sequences were mapped on the dna. comparing the cleavage pattern of the ...1978212593
replication of nondefective parvoviruses: lack of a virion-associated dna polymerase.we have examined four of the nondefective parvoviruses for an associated dna polymerase. virions were purified from neuraminidase-treated infected-cell lysates by isopycnic centrifugation in cscl or from infected cell material by cacl(2) precipitation and centrifugation through sucrose into cscl. preparations of bovine parvovirus or kilham rat virus obtained by the former procedure contained dna polymerase activity but were not free of contaminating cellular proteins. the latter method produced ...1978212603
nucleotide sequence of the self-priming 3' terminus of the single-stranded dna extracted from the parvovirus kilham rat virus.the parvovirus genome is a linear, single-stranded dna molecule with double-stranded hairpin termini. the 3' terminus can serve in vitro as a self-primer for the synthesis of a double-stranded viral dna intermediate. we have sequenced the nucleotides in the 3' terminus and propose a model for the secondary structure of the terminus and the in vitro origin of replication for the complementary viral dna strand.1979225552
characterization of the deoxyribonucleic acid polymerase associated with kilham rat virus.purified preparations of the parvovirus, kilham rat virus, have associated with them a protein with dna polymerase activity. the enzyme has been separated from the other two or three viral proteins and purified 63-fold. the viral associated enzyme was found in a single peak of dna polymerase activity after chromatography on deae-cellulose, dna-cellulose, and phosphocellulose columns. it shares some properties in common with the host cellular dna polymerases, described in the preceding paper (sal ...1975237924
sequence of the 3' terminus of the genome from kilham rat virus, a nondefective parvovirus. 1979462820
inhibition of in vitro lymphoproliferative responses by in vivo passaged rat 13762 mammary adenocarcinoma cells. ii. evidenceth kilham rat virus is responsible for the inhibitory effect. 1977912764
immunosuppressive activity of a subline of the mouse el-4 lymphoma. evidence for minute virus of mice causing the inhibition.filtered culture fluids from the early in vitro passages of a subline of the c57bl/6 mouse el-4 lymphoma, el-4(g-), were strongly inhibitory for babl/c vs. c57bl/6 mixed lymphocyte cultures (mlc). the inhibitory activity could be preserved by storage at -75 degrees c or 4 degrees c, thus allowing its further characterization. the inhibitory factor was particulate (nondialyzable, sedimentable at 100,000 g for 1 h), very small (recovered after 0.10 mum filtration), sensitive to uv irradiation, but ...19761244418
effect of spontaneous pathology and thrombin on leukocyte adhesion to rat aortic endothelium.leukocyte adhesion and other injury parameters have been studied in the aortic endothelium of sprague-dawley rats in two situations: (1) spontaneous pathology in conventional rats with antibodies to mycoplasma pulmonis and/or kilham or sendai viruses, and (2) intravascular coagulation by thrombin administration in spf rats. adhesion (esterase (+) leukocytes/mm2) in spf rats was 8 +/- 5 (n = 12). adhesion in 38% of the conventional rats was 54 +/- 27 (n = 8), half of them being non-analyzed and t ...19921590826
altered lipid metabolism in parvovirus-infected cells.a broad spectrum of cell lipid alterations are known to occur as a consequence of various viral infections. these changes include inhibition of lipid synthesis, stimulation of lipid synthesis and changes in the proportions of various lipids. the current study examined the effects of two parvoviruses on lipids of rat kidney (nrk) cells. cells were infected with h-1 or kilham rat virus (krv) and the effects on 14c-acetate incorporation determined. results showed that h-1 virus rapidly inhibited li ...19911865833
seromonitoring in small laboratory animal colonies. a five year survey: 1984-1988.from 1984 to 1988 one thousand serologic investigations of laboratory animal colonies originating from 10 different european countries were performed. the most prevalent infections in mouse stocks were caused by mouse hepatitis virus (mhv), minute virus of mice (mvm), theiler's encephalomyelitis virus (temv), reovirus type 3 (reo3), sendaivirus, and pneumonia virus of mice (pvm). in mice no infections with lymphocytic choriomeningitis virus (lcm), polyomavirus, mouse adenovirus, and k-virus were ...19902321435
antigenic relationships among autonomous parvoviruses.the antigenic relatedness of minute virus of mice (mvm), kilham rat virus (kr), h-1 virus (h-1), haemorrhagic encephalopathy of rats virus (her), porcine parvovirus (ppv), canine parvovirus (cpv), feline panleukopenia virus (fpv), goose parvovirus (gpv) and bovine parvovirus (bpv) was studied by immunofluorescence microscopy (fa) and by serum neutralization (sn). an antigenically related group comprising mvm, kr, her, ppv, cpv and fpv was recognized by fa and most reactions within the group were ...19862432167
porcine parvovirus: dna sequence and genome organization.we have determined the nucleotide sequence of an almost full-length clone of porcine parvovirus (ppv). the sequence is 4973 nucleotides (nt) long. the 3' end of virion dna shows a y-shaped configuration homologous to rodent parvoviruses. the 5' end of virion dna shows a repetition of 127 nt at the carboxy terminus of the capsid proteins. the overall organization of the ppv genome is similar to those of other autonomous parvoviruses. there are two large open reading frames (orfs) that almost enti ...19892794971
isolation and characterization of thermosensitive mutants from kilham rat virus, a rodent parvovirus.thermosensitive mutants were isolated from nitrous acid-treated kilham rat virus (krv). at a restrictive temperature (39.5 degrees c), the mutants tested did not produce appreciable amounts of infectious particles, haemagglutinin or progeny single-stranded dna. virus antigen accumulation as detected by immunoperoxidase was reduced. complementation tests revealed two distinct groups. the three members of complementation group 1 synthesized normal amounts of replicative forms but were restricted i ...19882826664
adhesion of leukocytes to the aortic endothelium of conventional, specific pathogen free (spf) and hypercholesterolemic spf rats.adhesion of leukocytes to the aortic endothelium was studied in specific pathogen-free (spf) and conventional rats and in spf rats with diet-induced hypercholesterolemia. nonspecific esterase activity with alpha-naphthyl acetate as substrate was used to characterize the adhered cells. phagocytic activity was determined by injecting i.v. 0.1-0.4 ml/100 g doses of monastral blue b (mbb). adhesion in spf rats was 8 +/- 4 esterase (+) cells/mm2. adhesion in conventional rats was of the same order ex ...19892930616
a serological survey on 15 murine pathogens in mice and rats.a serological survey for 15 murine pathogens was performed on 269 mouse sera collected from 21 conventional and 12 barrier colonies, and on 376 rat sera collected from 21 conventional and 23 barrier colonies. animals having an antibody against at least one of the antigens were contained in 81.0% of conventional and 16.7% of barrier mouse colonies and also in 81.0% of conventional and 43.5% of barrier rat colonies. main contaminants were mouse hepatitis virus and sendai virus in mice, and sendai ...19863026818
virucidal efficacy of physico-chemical treatments against coronaviruses and parvoviruses of laboratory animals.virucidal efficacy of chemical disinfectants, heating and ultraviolet radiation against mouse hepatitis virus (mhv), canine coronavirus (ccv), kilham rat virus (krv) and canine parvovirus (cpv) were examined. coronaviruses (mhv and ccv) were inactivated by ethanol, isopropanol, benzalkonium chloride, iodophor, sodium hypochlorite, sodium chlorite, cresol soap and formaldehyde as well as by heating at 60 degrees c for 15 minutes, whereas parvoviruses (krv and cpv) appeared to be inactivated by di ...19883416941
proteins tightly associated with the termini of replicative form dna of kilham rat virus, an autonomous parvovirus.revie et al. [revie, d., tseng, b. y., grafstrom, r. h. & goulian, m. (1979) proc. natl. acad. sci. usa 76, 5539-5543] have proposed that the double-stranded replicative form (rf) dna of the autonomous rodent parvovirus h-1 has protein of 60 kda covalently bound at its 5' termini. we present evidence that the rf dna of a similar rodent parvovirus, kilham rat virus (krv), also has covalently bound protein. nadodso4/polyacrylamide gel electrophoresis of purified, 125i-labeled rf dna shows that pro ...19853866226
characterization of the kilham rat virus.kilham rat virus (krv) was found to grow in a rat nephroma cell line and to form plaques on secondary rat embryo monolayers. the virus was purified by enzymatic treatment and isopycnic cesium chloride sedimentation. krv bands at a density of 1.41 g/cm(3) in cesium chloride. it contains about 26.5% deoxyribonucleic acid (dna). the sedimentation coefficient s(20,w) in sucrose gradients was 122 corresponding to a molecular weight of 6.6 x 10(6) daltons. the reaction of formaldehyde with the krv vir ...19704317344
structural proteins of kilham rat virus. 19704321164
linear, single-stranded deoxyribonucleic acid isolated from kilham rat virus.kilham rat virus (krv) was grown in a rat nephroma cell line and was purified by two isopycnic centrifugations in cesium chloride. the virus contains single-stranded deoxyribonucleic acid (dna) with a molecular weight of approximately 1.6 x 10(6). the dna was extracted from the virion by both phenol extraction and by 2% sodium dodecyl sulfate at 50 c. krv dna, extracted by both procedures, was observed in an electron microscope by using a cytochrome c or diethylaminoethyldextran monolayer. the d ...19714327590
growth characteristics of kilham rat virus and its effect on cellular cellular macromolecular synthesis.kilham rat virus (krv) is adsorbed into the rat nephroma cell within 1 hr after infection. there follows a latent period of about 12 hr during which less than 1% of the input infectious virus can be accounted for. new infectious virions can be detected at about 12 hr and the maximal yield of virus is attained by 23 hr after infection. the increase in final virus yield is about 200-fold over that found in the latent period. during this 23-hr period of virus growth, the rate of protein synthesis r ...19724343539
in vivo conversion of the single-stranded dna of the kilham rat virus to a double-stranded form.kilham rat virus (krv) contains linear, single-stranded dna in the virion. the fate of radioactive viral dna was followed after infection of monolayer cells. within 60 min after infection of cells, 28 to 42% of the parental viral dna is converted to a new form. this new dna form is believed to be double stranded and linear on the basis of its sedimentation in neutral and alkaline sucrose gradients, elution from hydroxyapatite columns, its buoyant density in equilibrium cscl density gradients, an ...19734347430
synthesis of viral-specific rna in cells infected with the parvovirus, kilham rat virus.we have studied the viral-specific rna synthesized after infection of a permissive cell line with kilham rat virus (krv). the rna was shown to be virus specific by analysis of its nucleotide base ratios and by hybridization with krv and cellular dna. viral rna is synthesized as early as 2 h after infection. this viral rna synthesis occurs before viral progeny dna synthesis which is initiated at 7 to 8 h after infection. the predominant viral rna synthesized before and after viral progeny dna syn ...19744369259
the replication of the kilham rat virus (rv) in various host systems: immunofluorescent studies. 19724622038
ultraviolet photobiology of kilham rat virus and the absolute ultraviolet photosensitivities of other animal viruses: influence of dna strandedness, molecular weight, and host-cell repair. 19724626463
purification of the kilham rat virus.a purification procedure is described for the isolation of kilham rat virus (rv) from infected suckling hamster kidney and liver suspensions. the procedure involved a combination of sonic treatment, differential centrifugation, butanol-chloroform extraction, agar column flow diffusion, and potassium tartrate density gradient centrifugation. the purified virus retained its infectivity and was specifically neutralized by rv hyperimmune antiserum. electron micrographs from the rv band (density 1.31 ...19674961932
studies on the natural infection of rats with the kilham rat virus. 19684969352
host influence on the antigenic composition of the kilham rat virus.the kilham rat virus (rv) was found to vary in infectivity and antigenic characteristics when propagated in two different host systems. both cross hemagglutination-inhibition (hi) and cross virus-neutralization tests revealed that a nonreciprocal or one way cross exists between rv propagated in rat embryo cell cultures (re-rv) and rv propagated in suckling hamsters (h-rv). specifically, immune serum to re-rv inhibited hemagglutination and infectivity by both viruses to the same extent. immune se ...19694982829
requirement of cellular synthesis for kilham rat virus replication. 19704992351
inhibition of mitosis and macromolecular synthesis in rat embryo cells by kilham rat virus.the effects of kilham rat virus multiplication were studied in cultured rat embryo cells to examine the mechanisms by which virus infection might be related to developmental defects in rats and hamsters. the virus was found to inhibit motosis and deoxyribonucleic acid (dna) synthesis within 2 to 10 hr after infection. however, total ribonucleic acid synthesis was relatively unaffected until about 20 hr after infection, and total protein synthesis did not decline significantly until loss of viabl ...19715167023
dna polymerase activity associated with purified kilham rat virus. 19715281195
the dna of kilham rat virus. 19705417272
single-stranded dna from the kilham rat virus. 19695772490
enzyme-linked immunosorbent assay in the diagnosis of kilham rat virus infection in rats.an enzyme-linked immunosorbent assay (elisa) was adapted and compared with the haemagglutination-inhibition (hai) test for the serological diagnosis of kilham rat virus (krv) infection in rats. the assay is a solid phase, indirect method for the measurement of specific antibody. test variables such as the amount of purified krv for coating polystyrene microtitre plates, dilution of peroxidase conjugate, etc. were standardized for optimum results. sera from both naturally and experimentally infec ...19846096629
effects of kilham rat virus on natural killer cell-mediated cytotoxicity in brown norway and wistar furth rats.effects of kilham rat virus (krv) on selected aspects of the immune response of 2 strains of laboratory rats were studied. the brown norway rat and wistar furth rat were infected with krv and serum antibody and interferon values and cytotoxic activity of natural killer cells were determined to assess the virus' effect on the rat's immune systems. antibody values to the virus were increased in both strains after viral inoculation, and total antibody values were comparable in the 2 rat strains. na ...19846200013
comparative inactivation of viruses by chlorine.the kinetics of inactivation of six enteric viruses plus simian virus 40 and kilham rat virus by free available chlorine was studied under carefully controlled laboratory conditions. it was found that the different virus types demonstrated a wide range of susceptibility to chlorine disinfection. the rate of inactivation was greater at ph 6 than at ph 10; however, the relative susceptibilities of the different viruses were affected differently by a change in ph, suggesting that the ph influenced ...19806258473
restriction map of the single-stranded dna genome of kilham rat virus strains 171, a nondefective parvovirus.we constructed a physical map of kilham rat virus strains 171 dna by analyzing the sizes and locations of restriction endonuclease-generated fragments of the replicative-form viral dna synthesized in vitro. bgli, kpni, bamhi, smai, xhoi, and xorii did not appear to have any cleavage sites, whereas 11 other enzymes cleaved the genome at one to eight sites, and alui generated more than 12 distinct fragments. the 30 restriction sites that were mapped were distributed randomly in the viral genome. a ...19816270368
comparative physicochemical and biological properties of two strains of kilham rat virus, a non-defective parvovirus.two antigenically indistinguishable strains, 171 and 308, of kilham rat virus (krv) have distinct host ranges and contain capsid proteins of identical size, but with different isoelectric points. the single-stranded dna genomes of the viruses are also the same size but appear to have different secondary and tertiary structures. the genomes of the two strains have nearly identical cleavage maps of 11 restriction endonucleases, except for differences in five restriction sites in the region bracket ...19826288851
synthesis of mrna by the parvovirus krv in isolated nuclei.we have synthesized vial-specific transcripts in nuclei isolated from cells infected with the parvovirus kilham rat virus. radioactive vial-specific rna synthesized in the nuclei was extracted, hybridized to viral dna, incubated in glyoxal, and electrophoresed in an agarose gel. at least five viral-specific rnas were detected containing 4.6 kb (25-26s), 3.2 kb (major species, 20-22s), 2.9 kb, 1.3 kb, and 1.0 kb pairs. the 4.6 kb rna represents a transcript of 95-100% of the viral genome. the maj ...19826307256
kilham rat virus dna replication in subcellular fractions.a subcellular system actively replicating kilham rat virus dna in vitro was developed. cellular lysates and isolated nuclei from infected cells showed an amplification of replicative forms in vitro. solubilized replicative complexes, either partly purified or in the form of a crude extract, were able to synthesize replicative forms and single-stranded dna. dna polymerase alpha played a major role in kilham rat virus dna synthesis in vivo and in vitro. furthermore, a factor present in the cytosol ...19846438274
secondary infection of rat lungs with pasteurella pneumotropica after kilham rat virus infection.lung congestion was observed after an outbreak of kilham rat virus infection (krv) in a rat colony, previously free of all rat viruses. a high proportion of congested lungs contained pasteurella pneumotropica suggesting that krv might have caused primary damage to the alveoli (hitherto not recorded) which allowed the secondary bacterial colonization. experimental infection of rats with krv caused acute damage to the lung alveoli. since krv infection is very common in animal facilities it could t ...19816457220
structure of the capsid of kilham rat virus from small-angle neutron scattering.the structure of empty capsids of kilham rat virus, an autonomous parvovirus with icosahedral symmetry, was investigated by small-angle neutron scattering. from the forward scatter, the molecular weight was determined to be 4.0 x 10(6), and from the guinier region, the radius of gyration was found to be 105 a in d2o and 104 a in h2o. on the basis of the capsid molecular weight and the molecular weights and relative abundances of the capsid proteins, we propose that the capsid has a triangulation ...19846529570
peritoneal macrophages of pathogen-free rats but not of conventional rats secrete elastolytic activity.elicited peritoneal macrophages from sprague-dawley rats conventionally bred and housed failed, as we have reported, to produce detectable elastolytic activity in culture. they did produce lysozyme and plasminogen activator. we now show that in contrast to these cells, macrophages from pathogen-free, barrier-sustained rats produced readily demonstrable elastolytic activity. rats raised pathogen-free and subsequently housed conventionally for 2-4 wk appeared to lose the capacity to afford macroph ...19846589337
autonomous parvovirus luiii encapsidates equal amounts of plus and minus dna strands.autonomous parvoviruses are thought to uniquely encapsidate single-stranded dna of minus polarity. in contrast, the defective adeno-associated viruses separately encapsidate equal amounts of plus and minus dna strands. we reexamined the uniqueness of minus strand encapsidation for the autonomous parvoviruses. although we found that kilham rat virus and h-1 virus encapsidate varying but small amounts of complementary-strand dna, it was unexpected to find that luiii virus encapsidated equal amount ...19846694260
sequence homology between the structural proteins of kilham rat virus.the capsid proteins of the autonomous parvovirus kilham rat virus were purified and analyzed for peptide composition. partial proteolysis mapping and two-dimensional thin-layer chromatography of tryptic peptide digests revealed extensive amino acid sequence homology between the two major kilham rat virus capsid proteins.19846699933
electron microscopic comparison of the sequences of single-stranded genomes of mammalian parvoviruses by heteroduplex mapping.the sequence homologies among the linear single-stranded genomes of several mammalian parvoviruses have been studied by electron microscopic analysis of the heteroduplexes produced by reannealing the complementary strands of their dnas. the genomes of kilham rat virus, h-1, minute virus of mice and luiii, which are antigenically distinct non-defective parvoviruses, have considerable homology: about 70% of their sequences are conserved. the homologous regions map at similar locations in the left ...19836854648
detection of h-1 parvovirus and kilham rat virus by pcr.h-1 virus and kilham rat virus (krv) are autonomous parvoviruses which generally cause subclinical infections in rats and can cause persistent infections in cell cultures. in this study, primer sets specific for either h-1 or krv were designed on the basis of dna sequence comparisons of the rodent parvoviruses. the specificities of the h-1 and krv-specific primer sets were determined by testing viral preparations of seven different parvoviruses and nine other viruses known to infect rodents. the ...19957665631
preservation of glut 2 expression in islet beta cells of kilham rat virus (krv)-infected diabetes-resistant bb/wor rats.loss of glut 2, the glucose transporter isoform of pancreatic beta cells, has been reported to accompany the onset and perhaps contribute to the pathogenesis, of insulin-dependent and non-insulin-dependent diabetes mellitus in bb/wor and zucker fatty rats. in this study we investigated the effect of kilham rat virus infection on glut2 expression in diabetes-resistant bb/wor rats. viral antibody-free diabetes-resistant rats do not develop spontaneous diabetes, but inoculation with kilham rat viru ...19947895947
variability in the induction of experimental arthritis: yersinia associated arthritis in lewis rats.lewis rats of different microbiological status were studied for susceptibility to experimentally-induced yersinia associated arthritis. status a rats were serologically positive for bacillus piliformis, kilham rat virus and toolan h-1 virus, whereas status b rats were serologically negative for these same microorganisms. when status a and status b rats were kept in the same room, incidence of arthritis was low (0-13% for status a rats and 27-33% for status b rats). when status b rats only were k ...19948016582
diagnosis of kilham rat virus using pcr.the exclusive use of serology, namely immunofluorescent antibody (ifa), for the diagnosis of rodent parvovirus infection is limited to detecting igg antibodies which develop some time after the appearance of clinical symptoms, whilst conventional viral isolation, using tissue culture, is both expensive and time consuming. polymerase chain reaction (pcr) as a diagnostic method has the potential to overcome these problems. however, it requires detailed knowledge of the genetic code of the target o ...19948158965
contamination of transplantable tumors, cell lines, and monoclonal antibodies with rodent viruses.different biological materials were tested for murine viral contamination by using the mouse/rat antibody production test. of 297 tumors examined, 75 (25.3%) were contaminated. considerable differences in the contamination rate became evident when transplantable tumors from in vitro and from in vivo passages were compared. of 186 tumors that had been propagated in animals, 36.6% were positive, whereas only 7 of 111 (6.3%) tumors propagated in vitro were contaminated. the highest rate of contamin ...19938231085
infection of peripancreatic lymph nodes but not islets precedes kilham rat virus-induced diabetes in bb/wor rats.a parvovirus serologically identified as kilham rat virus (krv) reproducibly induces acute type i diabetes in diabetes-resistant bb/wor rats. the tissue tropism of krv was investigated by in situ hybridization with a digoxigenin-labelled plasmid dna probe containing approximately 1.6 kb of the genome of the umass isolate of krv. partial sequencing of the krv probe revealed high levels of homology to the sequence of minute virus of mice (89%) and to the sequence of h1 (99%), a parvovirus capable ...19938371347
yersinia associated arthritis in shr rats: effect of the microbial status of the host.following the intravenous injection of live yersinia enterocolitica o:8, 50-69% of shr rats developed arthritis; these rats were antibody free against all rat pathogens tested. in contrast, only 20-25% of shr rats which had serum antibodies against bacillus piliformis, kilham rat virus, and toolan h-1 virus developed arthritis. the results indicate that the microbial load of the host has a profound effect on the susceptibility to experimental arthritis.19938484677
kilham rat triggers t-cell-dependent autoimmune diabetes in multiple strains of rat.kilham rat virus (krv) infection of bb/wor diabetes-resistant (dr) rt1(u) rats induces autoimmune diabetes without direct cytolytic infection of pancreatic beta-cells and is a new model of virus-induced iddm. to investigate genetic susceptibility to krv-induced diabetes, major histocompatibility complex congenic and other inbred rats were infected with the virus and studied for the appearance of diabetes and insulitis. krv infection alone induced insulitis, selective beta-cell necrosis, and diab ...19968621003
role of macrophages and macrophage-derived cytokines in the pathogenesis of kilham rat virus-induced autoimmune diabetes in diabetes-resistant biobreeding rats.the diabetes-resistant biobreeding (dr-bb) rat, derived from diabetes-prone forebears, does not normally develop spontaneous insulitis or diabetes, but when infected with kilham rat virus (krv) this animal develops autoimmune diabetes similar to the diabetes-prone biobreeding (dp-bb) rat. in this study, we attempted to determine whether macrophages and macrophage-derived cytokines play a role in the development of krv-induced diabetes in dr-bb rats. seventy-eight percent of dr-bb rats treated wi ...19979200487
cellular and molecular mechanism for kilham rat virus-induced autoimmune diabetes in dr-bb rats.kilham rat virus (krv) causes autoimmune diabetes in diabetes-resistant biobreeding (dr-bb) rats; however, the mechanism by which krv induces autoimmune diabetes without the direct infection of beta cells is not well understood. we first asked whether molecular mimicry, such as a common epitope between a krv-specific peptide and a beta cell autoantigen, is involved in the initiation of krv-induced autoimmune diabetes in dr-bb rats. we found that krv peptide-specific t cells generated in dr-bb ra ...200010946320
the role of viruses in type i diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals.type i (insulin-dependent) diabetes mellitus results from the progressive loss of pancreatic beta cells. environmental factors are believed to play an important part in the development of type i diabetes by influencing the penetrance of diabetes susceptibility genes. as one environmental factor, the virus has long been considered to play a part in this disease. to date 13 different viruses have been reported to be associated with the development of type i diabetes in humans and in various animal ...200111317656
molecular characterization of three newly recognized rat parvoviruses.rodent parvoviruses have been documented to interfere with both in vivo and in vitro research. in this study, three rat parvoviruses distinct from previously characterized rodent parvoviruses were identified from naturally infected rats obtained from four discrete sources. these three newly recognized parvoviruses were designated rat minute virus (rmv)-1a, -1b and -1c. in this study, the genomic nucleotide sequence and the predicted amino acid sequences of proteins for each of the three rmv-1 va ...200212124471
a new look at viruses in type 1 diabetes.type 1 diabetes (t1d) results from the destruction of pancreatic beta cells. genetic factors are believed to be a major component for the development of t1d, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. viruses are one environmental factor that is implicated in the pathogenesis of t1d. to date, 14 different viruses have been reported to be associated with ...200312592641
isolation of virus-like particles associated with kilham rat virus infection of tissue cultures. 196414240408
[development of an antigen for the diagnosis of kilham rat parvovirus by hemagglutination inhibition test].an antigen of rat parvovirus (kilham virus) was developed for the diagnosis of viral infection in rat colonies by using hemagglutination inhibition (hai) test. primary cell cultures from rat embryos were infected with kilham rat virus. infected cells obtained at different time post infection were scraped, centrifuged, concentrated one hundred times, sonicated and centrifuged again. the supernatants obtained were titrated by hemagglutination. the specificity was confirmed with positive and negati ...200415174744
viruses in type 1 diabetes: brief review.type 1 diabetes results from the progressive destruction of insulin-producing pancreatic beta cells. although the etiology of type 1 diabetes is believed to have a major genetic component, studies on the risk of developing type 1 diabetes suggest that environmental factors, such as viruses, may be important etiological determinants. among the viruses, the most clear and unequivocal evidence that a virus induces type 1 diabetes in animals comes from studies on the d variant of encephalomyocarditi ...200415229381
immunoregulatory role of nitric oxide in kilham rat virus-induced autoimmune diabetes in dr-bb rats.macrophages play a critical role in the pathogenesis of kilham rat virus (krv)-induced autoimmune diabetes in diabetes-resistant biobreeding (dr-bb) rats. this investigation was initiated to determine the role of macrophage-derived soluble mediators, particularly no, in the pathogenesis of krv-induced diabetes in dr-bb rats. we found that the expression of inducible no synthase (inos), an enzyme responsible for no production, was significantly increased during the early phase of krv infection. i ...200415240727
tlr activation synergizes with kilham rat virus infection to induce diabetes in bbdr rats.virus infection is hypothesized to be an important environmental "trigger" of type 1 diabetes in humans. we used the bbdr rat model to investigate the relationship between viral infection and autoimmune diabetes. bbdr rats are diabetes-free in viral ab-free housing, but the disease develops in approximately 30% of bbdr rats infected with kilham rat virus (krv) through a process that does not involve infection of pancreatic beta cells. pretreatment with polyinosinic-polycytidylic (poly(i:c)), a l ...200515611235
the rat diabetes susceptibility locus iddm4 and at least one additional gene are required for autoimmune diabetes induced by viral infection.bbdr rats develop autoimmune diabetes only after challenge with environmental perturbants. these perturbants include polyinosinic:polycytidylic acid (poly i:c, a ligand of toll-like receptor 3), agents that deplete regulatory t-cell (treg) populations, and a non-beta-cell cytopathic parvovirus (kilham rat virus [krv]). the dominant diabetes susceptibility locus iddm4 is required for diabetes induced by treatment with poly i:c plus treg depletion. iddm4 is penetrant in congenic heterozygous rats ...200515793267
pathogenesis and transmission of kilham rat virus infection in rats.the kilham rat virus (rv) was found to produce mortality in newborn rats after intracerebral, intravenous, or subcutaneous administration of virus. both infectious virus and viral hemagglutinins were detected in a variety of tissues and in the blood and urine of experimentally infected rats. contact control rats housed with infected littermates did not develop disease but did produce antibody to rv. horizontal virus transmission was also evidenced by the seroconversion of antibody-negative mothe ...197016557835
development of elisa using recombinant antigens for specific detection of mouse parvovirus infection.nucleotide sequences of mouse parvovirus (mpv) isolate, named mpv/ut, and mouse minute virus (mmv) were analyzed and used for expressing recombinant proteins in e. coli. elisa tests using recombinant major capsid protein (rvp2) and recombinant major non-structural protein (rns1) as antigens were developed and their performance in serologic detection of rodent parvovirus infection was assessed. mpv-rvp2 and mmv-rvp2 elisas reacted specifically with anti-mpv and anti-mmv mouse sera, respectively. ...200616651694
persistent infection of a rat nephroma cell line with kilham rat virus.a rat nephroma cell line was found to be a carrier culture of the kilham rat virus. infectious virus was demonstrable only by passage of culture materials into other host systems.196916789110
short regions of sequence identity between the genomes of human and rodent parvoviruses and their respective hosts occur within host genes for the cytoskeleton, cell adhesion and wnt signalling.our understanding of the mechanism(s) of pathogenesis and persistence of vertebrate parvoviruses remains incomplete. with the recent availability of the complete genome sequences of human, rat and mouse, and the ability to search these sequences and to locate matches to exact genomic regions, further insight into the interaction of parvoviruses with their human and rodent hosts is possible. to determine the extent and nature of sequence identity between candidate parvoviruses and their respectiv ...200617098972
viruses cause type 1 diabetes in animals.more than 10 viruses have been reported to be associated with the development of type 1 diabetes-like symptoms in animals, with the best evidence coming from studies on the d variant of encephalomyocarditis (emc-d) virus in mice and kilham rat virus (krv) in rats. a high titer of emc-d viral infection results in the development of diabetes within 3 days, primarily due to the rapid destruction of beta cells by viral replication within the cells. a low titer of emc-d viral infection results in the ...200617130545
tlr9-signaling pathways are involved in kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat.viral infections are associated epidemiologically with the expression of type 1 diabetes in humans, but the mechanisms underlying this putative association are unknown. to investigate the role of viruses in diabetes, we used a model of viral induction of autoimmune diabetes in genetically susceptible biobreeding diabetes-resistant (bbdr) rats. bbdr rats do not develop diabetes in viral-ab-free environments, but approximately 25% of animals infected with the parvovirus kilham rat virus (krv) deve ...200717202329
a survey of rodent-borne pathogens carried by wild-caught norway rats: a potential threat to laboratory rodent colonies.unintentional infection of laboratory rodents can compromise scientific research as well as the health of the animals and animal handlers. the source of contamination often is unknown, but may be introduced by wild rats from surrounding environments. to determine whether rats in baltimore, maryland, usa carry infectious agents commonly found in laboratory rodent colonies, we live-trapped 162 rats during 2005 to 2006 and screened them for a panel of viruses, bacteria and parasites. antibodies aga ...200818348770
innate immune pathways in virus-induced autoimmune diabetes.we recently hypothesized that toll-like receptor-induced innate upregulation by kilham rat virus (krv) in the biobreeding diabetes-resistant (bbdr) rat model plays a key role in the mechanism of diabetes induction. to address this hypothesis, we analyzed innate immune signaling pathways upregulated by krv in vitro and in vivo. we demonstrate that krv activates the signal transducer and activator of transcription (stat)-1 in spleen cells in vitro and that this activation can be blocked by tlr9 in ...200819120282
a serological survey to evaluate contemporary prevalence of viral agents and mycoplasma pulmonis in laboratory mice and rats in western europe.to evaluate current prevalence rates of 24 viruses and of the bacterium mycoplasma pulmonis, the authors retrospectively surveyed serological data obtained from laboratory mice and rats housed in more than 100 western european institutions. serum samples were submitted to the authors' institution for testing between january 2007 and june 2008. the prevalence of an infection was defined as the percentage of tested samples that yielded positive results for a specific agent. in mice, the most commo ...200919384313
failure of alpha-galactosylceramide to prevent diabetes in virus-inducible models of type 1 diabetes in the rat.alpha-galactosylceramide (alpha-galcer) is an invariant natural killer t (inkt) cell ligand that prevents type 1 diabetes in nod mice. however, alpha-galcer can activate or suppress immune responses, raising concern about its potential use in human diabetes.200919414403
microbial contaminations of laboratory mice and rats in taiwan from 2004 to 2007.limited data are available on the pathogen status of contemporary rodent colonies in taiwan. here we summarized the rodent pathogen diagnostic records of the taiwan national laboratory animal center during a 4-y period that representing approximately 10% of the rodent colonies in taiwan. demand for pathogen diagnostic service increased continuously from 2004 to 2007, with a 20% increase each year. in 2007, more than 20% of the mouse colonies were positive for mouse parvovirus, mouse hepatitis vi ...200919653946
virus-induced autoimmune diabetes in the lew.1wr1 rat requires iddm14 and a genetic locus proximal to the major histocompatibility complex.to identify genes that confer susceptibility to autoimmune diabetes following viral infection in the lew.1wr1 rat.200919720792
infection with viruses from several families triggers autoimmune diabetes in lew*1wr1 rats: prevention of diabetes by maternal immunization.the contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes.201019794063
brief dexamethasone treatment during acute infection prevents virus-induced autoimmune diabetes.we used the lew1.wr1 rat to test the hypothesis that kilham rat virus-induced innate immune activation is involved in the mechanism of autoimmune diabetes. animals were treated with dexamethasone, an anti-inflammatory glucocorticoid, beginning on the day of infection. administering dexamethasone on five consecutive days completely blocked the disease. strikingly, a single dose of dexamethasone was sufficient to prevent islet destruction. dexamethasone downmodulated inflammation and restored norm ...201020167539
prevalence of antibodies against kilham virus in experimental rat colonies of argentina.the kilham rat virus (krv) is a parvovirus originally isolated from a rat sarcoma in the late 1950s. the clinical signs associated with a natural krv infection include foetal resorption in dams, runting, ataxia, cerebellar hypoplasia and jaundice in suckling rats, and sudden death, scrotal cyanosis, abdominal swelling and dehydration in juvenile rats. the ability of this virus to produce persistent infections has resulted in a high frequency of contamination of cell cultures and transplantable-t ...201020461290
leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in bb rats.the adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. we hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. nearly 100% of weanling bbdr rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pic), and kilham rat virus (krv) become diabetic within ...201120695765
haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and lew1.wr1 rats.proteomic profiling of serum is a powerful technique to identify differentially expressed proteins that can serve as biomarkers predictive of disease onset. in this study, we utilized two-dimensional (2d) gel analysis followed by matrix-assisted-laser desorption/ionization time-of-flight mass spectrometry analysis to identify putative serum biomarkers for autoimmune type 1 diabetes (t1d) in biobreeding diabetes resistant (bbdr) rats induced to express the disease. treatment with toll-like recept ...201020975081
Innate immunity in type 1 diabetes.Rat models of diabetes have emerged as a powerful experimental tool for addressing the role of microbial pathogens in the mechanism of autoimmune diabetes. We have used the biobreeding diabetes resistant and LEW1.WR1 rat models to identify the role of virus-induced innate immunity in the mechanism of type 1 diabetes.201122069267
simultaneous detection of 4 prototypic rat parvoviruses using the luminex xtag assay in laboratory animal health monitoring.there are currently four rat parvoviruses including kilham rat virus (krv), toolans h-1 parvovirus (h-1virus), rat parvovirus type 1a (rpv-1a) and rat minute virus (rmv). virus detection methods are commonly based on conventional pcr - agarose gel electrophoresis or serological assay methods these methods are both time-consuming and lack specificity. in this study, we developed a bead array xtag assay for the simultaneous detection and discrimination of four rat parvoviruses. the detection limit ...201728577992
vp2 capsid domain of the h-1 parvovirus determines susceptibility of human cancer cells to h-1 viral infection.although h-1 parvovirus is used as an antitumor agent, not much is known about the relationship between its specific tropism and oncolytic activity. we hypothesize that vp2, a major capsid protein of h-1 virus, determines h-1-specific tropism. to assess this, we constructed chimeric h-1 viruses expressing kilham rat virus (krv) capsid proteins, in their complete or partial forms. chimeric h-1 viruses (ch1, ch2 and ch3) containing the whole krv vp2 domain could not induce cytolysis in hela, a549 ...201525857359
maternal treatment with short-chain fatty acids modulates the intestinal microbiota and immunity and ameliorates type 1 diabetes in the offspring.we recently hypothesized that the intestinal microbiota and the innate immune system play key roles in the mechanism of kilham rat virus-induced type 1 diabetes in the lew1.wr1 rat. we used this animal model to test the hypothesis that maternal therapy with short-chain fatty acids can modulate the intestinal microbiota and reverse virus-induced proinflammatory responses and type 1 diabetes in rat offspring. we observed that administration of short-chain fatty acids to rat breeders via drinking w ...201728886045
implication of the intestinal microbiome as a potential surrogate marker of immune responsiveness to experimental therapies in autoimmune diabetes.type 1 diabetes (t1d) is an autoimmune proinflammatory disease with no effective intervention. a major obstacle in developing new immunotherapies for t1d is the lack of means for monitoring immune responsiveness to experimental therapies. the lew1.wr1 rat develops autoimmunity following infection with the parvovirus kilham rat virus (krv) via mechanisms linked with activation of proinflammatory pathways and alterations in the gut bacterial composition. we used this animal to test the hypothesis ...201728301545
a critical role for the type i interferon receptor in virus-induced autoimmune diabetes in rats.the pathogenesis of human type 1 diabetes, characterized by immune-mediated damage of insulin-producing β-cells of pancreatic islets, may involve viral infection. essential components of the innate immune antiviral response, including type i interferon (ifn) and ifn receptor-mediated signaling pathways, are candidates for determining susceptibility to human type 1 diabetes. numerous aspects of human type 1 diabetes pathogenesis are recapitulated in the lew.1wr1 rat model. diabetes can be induced ...201727999109
the role of the intestinal microbiome in type 1 diabetes pathogenesis.the gastrointestinal system represents one of the largest interfaces between the human internal microenvironment and the external world. this system harbors trillions of commensal bacteria that reside in symbiosis with the host. intestinal bacteria play a crucial role in maintaining systemic and intestinal immune and metabolic homeostasis because of their effect on nutrient absorption and immune development and function. recently, altered gut bacterial composition (dysbiosis) was hypothesized to ...201627523648
kilham rat virus-induced type 1 diabetes involves beta cell infection and intra-islet jak-stat activation prior to insulitis.we used the lew1.wr1 rat model of kilham rat virus (krv)-induced type 1 diabetes (t1d) to test the hypothesis that disease mechanisms are linked with beta cell infection and intra-islet immune activation prior to insulitis. krv induces genes involved in type i and type ii interferon pathways in islet cell lines in vitro and in islets from day-5-infected animals in vivo via mechanisms that do not involve insulitis, beta cell apoptosis, or impaired insulin expression. immunohistochemistry studies ...201425129435
salicylate prevents virus-induced type 1 diabetes in the bbdr rat.epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. we used the virus-inducible biobreeding diabetes resistant (bbdr) rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (nsaid), to modulate development of type 1 diabetes. bbdr rats treated with kilham rat virus (krv) and polyinosinic:polycytidylic acid (pic, a tlr3 agonist) develop diabetes at nearly 100% incidence by ~2 weeks. w ...201324147110
modulation of virus-induced innate immunity and type 1 diabetes by il-1 blockade.we used the lew1.wr1 model of kilham rat virus (krv)-induced type 1 diabetes (t1d) to test the hypothesis that blocking il-1 pathways early in the course of the disease can modulate virus-induced innate immunity and prevent disease progression. administering krv plus il-1 receptor antagonist (anakinra) for 14 d prevented insulitis and t1d. anakinra reversed the krv-induced systemic inflammation evidenced by the accumulation of t cells in the spleen and pancreatic lymph nodes on d 5 post-infectio ...201424062197
histone deacetylase inhibitor suppresses virus-induced proinflammatory responses and type 1 diabetes.microbial infections are hypothesized to play a key role in the mechanism leading to type 1 diabetes (t1d). we used the lew1.wr1 rat model of kilham rat virus (krv)-induced islet destruction to better understand how virus infection triggers t1d. inoculation of the lew1.wr1 rat with krv results in systemic inflammation followed by insulitis and islet destruction 2-4 weeks post-infection. in this study, we evaluated the effect of treatment with the anti-inflammatory histone deacetylase inhibitor ( ...201423982318
prevention of virus-induced type 1 diabetes with antibiotic therapy.microbes were hypothesized to play a key role in the progression of type 1 diabetes (t1d). we used the lew1.wr1 rat model of kilham rat virus (krv)-induced t1d to test the hypothesis that the intestinal microbiota is involved in the mechanism leading to islet destruction. treating lew1.wr1 rats with krv and a combination of trimethoprim and sulfamethoxazole (sulfatrim) beginning on the day of infection protected the rats from insulitis and t1d. pyrosequencing of bacterial 16s rrna and quantitati ...201222988033
seroprevalence of rodent pathogens in wild rats from the island of st. kitts, west indies.a pilot seroprevalence study was conducted to document exposure to selected pathogens in wild rats inhabiting the caribbean island of st. kitts. serum samples collected from 22 captured wild rats (rattus norvegicus and rattus rattus) were tested for the presence of antibodies to various rodent pathogens using a rat mfi2 serology panel. the samples were positive for cilia-associated respiratory bacillus (13/22; 59.1%), clostridium piliforme (4/22; 18.2%), mycoplasma pulmonis (4/22; 18.2%), pneumo ...201931083284
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