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transcription map and expression of bovine herpesvirus-1 glycoprotein d in early region 4 of bovine adenovirus-3.early region 4 (e4) of bovine adenovirus type 3 (bav-3) was analyzed by northern blotting, rt-pcr analysis, cdna sequencing, and s1 nuclease protection assays. the transcriptional map of the e4 region of bav-3 has marked dissimilarities from those of mouse adenovirus-1, ovine adenovirus-287, and human adenovirus-2, for which the transcriptional maps have been constructed. the e4 region of bav-3, located between 98.6 and 89.8 mu transcribes seven distinct classes of bovine adenovirus type 3 mrna. ...199910441562
mouse adenovirus (mav-1) expression in primary human endothelial cells and generation of a full-length infectious plasmid.using rt-pcr, we show that mouse adenovirus type i (mav-1) is capable of infecting and expressing in various cell types, specifically human endothelial cells. the capability of mav-1 to infect and express in human endothelial cells makes it a potentially useful alternative to the use of human adenoviruses type 2/5 (ad2/5) in virus-based gene therapy, although presently mav-1 can only be produced at lower titers than ad2/5. in this report, we present methods for the purification of mav-1 dna and ...199910455438
in vitro and in vivo characterization of a mouse adenovirus type 1 early region 3 null mutant.previous attempts to construct a mouse adenovirus type 1 early region 3 (e3) null mutant by initiator codon mutagenesis were unsuccessful because one of the e3 proteins, gp11k, is synthesized as a fusion protein from a late viral mrna (a. n. cauthen and k. r. spindler, virology 259:119-128, 1999). therefore, a different mutagenesis strategy was employed that inserted termination codons into all three reading frames of the e3 proteins. this strategy produced a mutant, pme314, that was null for th ...199910482617
the distribution and kinetics of polyomavirus in lungs of intranasally infected newborn mice.the primary cell types that sustain polyomavirus (py) replication following intranasal infection as well as the nature of the host cellular response to py were unknown. as this is an essential and specific site for virus entry, it seems likely that viral gene function must be adapted to these mucosal tissues. using immunohistochemistry and in situ hybridization, we determined the cell types in the lung that support py gene expression and replication following intranasal inoculation of newborn mi ...200010612660
ifn-gamma-independent igg2a production in mice infected with viruses and parasites.after infection with some viruses and intracellular parasites, antibody production is restricted to igg2a. we first observed that, whereas live viruses such as lactate dehydrogenase-elevating virus (ldv) or mouse adenovirus induced mostly an igg2a response, a large proportion of antibodies produced against killed viruses were igg1. this igg1 antiviral response was suppressed when live virions were added to inactivated viral particles. these results indicate that the igg2a preponderance is relate ...200010653858
cytokine, chemokine and chemokine receptor mrna expression in different strains of normal mice: implications for establishment of a th1/th2 bias.the resistance or susceptibility of inbred strains of mice to various pathogens and autoimmune diseases such as eae has been linked to differences in the balance between cytokines associated with th1- and th2-type immune responses. previous work from this laboratory on the mouse strain specific resistance to mouse adenovirus type i (mav-1)-induced encephalopathy revealed subtle differences in the transcription rates of several immunologically important molecules that was evident prior to infecti ...199910695717
mouse adenovirus type 1 replication in vitro is resistant to interferon.the effects of mouse interferon (ifn)-alpha/beta and recombinant ifn-gamma on mouse adenovirus type 1 (mav-1) replication were investigated in single-cycle infectious virus yield reduction assays on mouse l929 cells. viral yields at 3 days postinfection indicated that wt mav-1 and pme314, an early region 3 null mutant, were relatively insensitive to both ifn-alpha/beta and ifn-gamma, whereas early region 1a (e1a) mutants pme109 (null), dle105 (conserved region 1 deletion, cr1 delta), dle102 (cr2 ...200010936102
evidence for mimicry by viral antigens in animal models of autoimmune disease including myocarditis.molecular mimicry of viral antigens with self determinants has been proposed as one of the pathogenic mechanisms in autoimmune disease. evidence of viral mimicry in animal models of autoimmunity is accumulating. murine adenovirus, semliki forest virus, lactate dehydrogenase-elevating virus, herpes simplex virus type-1, hepatitis b virus, encephalomyocarditis virus, theiler's murine encephalomyelitis virus, coxsackievirus and cytomegalovirus have been found to mimic physiologically important host ...200011130455
complete nucleotide sequence of the mycoplasma virus p1 genome.mycoplasma virus p1 is one of only four viruses isolated from the genus mycoplasma. the host for p1, mycoplasma pulmonis, possesses complex, phase-variable restriction and modification enzymes and the vsa family of phase-variable surface proteins. the ability of p1 virus to infect host cells is influenced by these phase-variable systems, rendering p1 a valuable tool for assessing host properties. the double-stranded p1 dna genome was sequenced (11,660 bp) and 11 orfs were identified. the predict ...200111322826
retargeting of viral vectors to the folate receptor endocytic pathway.viral vectors with high transfection efficiencies are not always those with optimal target cell binding specificities. as a consequence, virus pseudotyping has been developed to endow transfection competent viruses with improved cell binding specificities and affinities. we have hypothesized that chemical conjugation of a virus to a cell specific ligand might also alter its target cell specificity and produce a virus that would transfect only the desired cell type. to test this concept, an ecotr ...200111489485
sjl/j mice are highly susceptible to infection by mouse adenovirus type 1.mouse adenovirus type 1 (mav-1) targets endothelial and monocyte/macrophage cells throughout the mouse. depending on the strain of mouse and dose or strain of virus, infected mice may survive, become persistently infected, or die. we surveyed inbred mouse strains and found that for the majority tested the 50% lethal doses (ld(50)s) were >10(4.4) pfu. however, sjl/j mice were highly susceptible to mav-1, with a mean ld(50) of 10(-0.32) pfu. infected c3h/hej (resistant) and sjl/j (susceptible) mic ...200111711594
serological evidence of murine pathogens in wild grey squirrels (sciurus carolinensis) in north wales.wild grey squirrels in north wales were examined for their serological response to a range of laboratory mouse pathogens. nineteen squirrels were tested against 14 organisms and a high seroprevalence was found to several, including murine cytomegalovirus, mouse adenovirus, reovirus 3, rotavirus and sendai virus. four of the squirrels were seropositive for lymphocytic choriomeningitis virus, a zoonotic pathogen. none of the infections has previously been reported in squirrels.200212019534
t cells cause acute immunopathology and are required for long-term survival in mouse adenovirus type 1-induced encephalomyelitis.infection of adult c57bl/6 (b6) mice with mouse adenovirus type 1 (mav-1) results in dose-dependent encephalomyelitis. utilizing immunodeficient mice, we analyzed the roles of t cells, t-cell subsets, and t-cell-related functions in mav-1-induced encephalomyelitis. t cells, major histocompatibility complex (mhc) class i, and perforin contributed to acute disease signs at 8 days postinfection (p.i.). acute mav-1-induced encephalomyelitis was absent in mice lacking t cells and in mice lacking perf ...200312941916
propagation of mouse adenovirus on cell lines of human origin. 196414207231
increased susceptibility of mice infected with mouse adenovirus to escherichia coli-induced pyelonephritis.mouse adenovirus causes a persistent infection in the mouse kidney that produces extensive mononuclear cell infiltrates in cortex and medulla. tubular necrosis, dilatation, and occasional collapse occur but no glomerular changes or periglomerular fibrosis have been observed. acute and chronic adenovirus infection of the kidney predispose the kidney to develop acute pyelonephritis when the mouse is challenged by the intravenous or retrograde route with escherichia coli.196414238929
deletions within the u3 long terminal repeat alter the tumorigenic potential of myeloblastosis associated virus type 1(n).the molecularly cloned myeloblastosis-associated virus type-1(n) (mav-1(n)) strain induces specifically nephroblastomas in chicken. mav-induced nephroblastoma constitutes a unique animal model of the human wilms' tumor. we have previously shown that the mav-1(n) long terminal repeats (ltr) were necessary and sufficient for nephroblastoma induction. since major determinants for oncogenesis have been mapped in the u3 region of several other retroviruses, we have analyzed the tumorigenic potential ...200314599793
fatal disseminated mouse adenovirus type 1 infection in mice lacking b cells or bruton's tyrosine kinase.mouse adenovirus type 1 (mav-1) infection of b-cell-deficient and bruton's tyrosine kinase (btk)-deficient mice resulted in fatal disseminated disease resembling human adenovirus infections in immunocompromised patients. mice lacking b cells or btk were highly susceptible to acute mav-1 infection, in contrast to controls and mice lacking t cells. to our knowledge, this is the first demonstration that mice with an x-linked immunodeficiency phenotype (btk deficient) are susceptible to virus-induce ...200415140955
rederivation of transgenic and gene-targeted mice by embryo transfer.research on genetically engineered mice provides insights into the etiology, therapy, and genetic basis of human diseases. an important variable that affects the results of mouse studies is the health status of the animals. pathogen burdens may confound observations and obscure underlying mechanisms. mouse resource centers frequently rederive infected mouse strains. we review our experience on the use of a well-established technique, embryo transfer to rederive infected mouse strains. the follow ...200415517995
requirement of sur2 for efficient replication of mouse adenovirus type 1.mouse adenovirus type 1 (mav-1) early region 1a (e1a) encodes a virulence gene in viral infection of mice. to broaden our understanding of the functions of e1a in mav-1 pathogenesis, an unbiased experimental approach, glutathione s-transferase (gst) pulldown, was used to screen for cellular proteins that interact with e1a protein. we identified mouse sur2, a subunit of mediator complex, as a protein that binds to mav-1 e1a. the interaction between sur2 and mav-1 e1a was confirmed in virus-infect ...200415542641
characterization of virus isolates by particle-associated nucleic acid pcr.diagnostic virus isolation is still frequently used, particularly from respiratory tract secretions. testing positive virus cultures for all possible viruses is time-consuming, and unexpected or unknown viruses may escape detection. therefore, a novel random pcr approach was developed that allows sequence-independent amplification of viral nucleic acids from virus isolation-positive cultures. selectivity for viral sequences is obtained by preferential isolation of nucleic acids that are particle ...200515695669
e1a-cr3 interaction-dependent and -independent functions of msur2 in viral replication of early region 1a mutants of mouse adenovirus type 1.msur2, a subunit of the mediator complex, is required for efficient mouse adenovirus type 1 (mav-1) replication (l. fang, j. l. stevens, a. j. berk, and k. r. spindler, j. virol. 78:12888-12900, 2004). we examined the contributions of early-region 1a (e1a) to msur2 function in mav-1 replication with e1a mutant viruses. at a multiplicity of infection (moi) of 1, viruses containing cr3 replicated better in sur2+/+ mouse embryonic fibroblasts (mefs) than in sur2-/- mefs. in contrast, viruses lackin ...200515731221
acute respiratory infection with mouse adenovirus type 1.studies of the pathogenesis of adenovirus respiratory disease are limited by the strict species-specificity of the adenoviruses. following intranasal inoculation of adult c57bl/6 mice with mouse adenovirus type 1 (mav-1), we detected mav-1 early region 3 (e3) and hexon gene expression in the lungs at 7 days post-infection (dpi). we detected mav-1 e3 protein in the respiratory epithelium at 7 dpi. we did not detect viral mrna or protein at 14 dpi, but mav-1 dna was detected by pcr at 21 dpi. chem ...200516054189
identification of quantitative trait loci for susceptibility to mouse adenovirus type 1.adult sjl/j mice are highly susceptible to mouse adenovirus type 1 (mav-1) infections, whereas other inbred strains, including balb/cj, are resistant (k. r. spindler, l. fang, m. l. moore, c. c. brown, g. n. hirsch, and a. k. kajon, j. virol. 75:12039-12046, 2001). using congenic mouse strains, we showed that the h-2(s) haplotype of sjl/j mice is not associated with susceptibility to mav-1. susceptibility of mav-1-infected (balb/cj x sjl/j)f(1) mice was intermediate between that of sjl/j mice an ...200516103204
mouse adenovirus type 1 infection in scid mice: an experimental model for antiviral therapy of systemic adenovirus infections.the importance of human adenovirus infections in immunocompromised patients urges for new and adequate antiadenovirus compounds. since human adenoviruses are species specific, animal models for systemic adenovirus infections rely on a nonhuman adenovirus. we established mouse adenovirus type 1 (mav-1) infection of balb/c scid mice as a model for the evaluation of antiadenovirus therapy. in vitro studies with mouse embryonic fibroblasts pointed to the acyclic nucleoside phosphonate cidofovir and ...200516251313
integration of myeloblastosis associated virus proviral sequences occurs in the vicinity of genes encoding signaling proteins and regulators of cell proliferation.myeloblastosis associated virus type 1 (n) [mav 1(n)] induces specifically nephroblastomas in 8-10 weeks when injected to newborn chicken. the mav-induced nephroblastomas constitute a unique animal model of the pediatric wilms' tumor. we have made use of three independent nephroblastomas that represent increasing tumor grades, to identify the host dna regions in which mav proviral sequences were integrated.200616403231
virus-induced specific cell surface antigen(s) on mouse adenovirus-infected cells.a virus-specific cell surface antigen(s) was detected on mouse adenovirus-infected cells by the immunofluorescent antibody technique. it was demonstrated in infected cells regardless of the mouse strain or animal species used. it became detectable on the cell surface about 6 h postinfection and was demonstrated in 90% of infected cells at 24 to 36 h postinfection. on the other hand, intracellular capsid antigens became detectable by the immunofluorescent antibody technique at about 24 h postinfe ...197716558120
mouse adenovirus type 1 attachment is not mediated by the coxsackie-adenovirus receptor.common human adenovirus (ad) vectors are derived from serotype 2 or 5, which use the coxsackie-adenovirus receptor (car) as their primary cell receptor. we investigated the receptor usage of mouse adenovirus type 1 (mav-1), which in vivo is characterized by a pronounced endothelial cell tropism. alignment of the fiber knob sequences of mav-1 and those of car-using adenoviruses, revealed that amino acid residues, critical for interaction with car, are not conserved in the mav-1 fiber knob. attach ...200616806202
sarcomas and myelocytomas induced by a retrovirus related to myeloblastosis-associated virus type 1 in white leghorn egg layer chickens.an outbreak of subcutaneous sarcomas in commercial white leghorn egg layers was observed in the northeastern united states during late 2004. subcutaneous tumors were confined to three flocks distributed in two locations and belonging to the same company. the tumors were first observed grossly by farm personnel at approximately 7 wk of age and persisted throughout the economic life of the flocks. most of the tumors observed during the growing period were present on the facial region or around the ...200616863068
contributions of e1a to mouse adenovirus type 1 pathogenesis following intranasal inoculation.we investigated the role of mouse adenovirus type 1 (mav-1) early region 1a (e1a) protein in adenovirus respiratory infection. intranasal (i.n.) inoculation of mice with wild type (wt) virus induced chemokine and cellular inflammatory responses in the lung. we observed similar responses in mice infected with an e1a-null mutant virus at the same dose, although the magnitude of these responses was lower. levels of viral hexon gene expression were lower in the lung following infection with e1a-null ...200716962154
construction of mouse adenovirus type 1 mutants.mouse adenovirus provides a model for studying adenovirus pathogenesis in the natural host. the ability to make viral mutants allows the investigation of specific mouse adenoviral gene contributions to virus-host interactions. methods for propagation and titration of wild-type mouse adenovirus, production of viral dna and viral dna-protein complex, and transfection of mouse cells to obtain mouse adenovirus mutants are described in this chapter. plaque purification, propagation, and titration of ...200717401163
capture elisa quantitation of mouse adenovirus type 1 in infected organs.a capture enzyme-linked immunosorbent assay (elisa) was optimized for identification of mouse adenovirus type 1 in infected brain homogenates. the elisa method allows for a much faster quantitation of virus in infected organs than plaque assays. methods for organ homogenization and the subsequent capture elisa are described in this chapter.200717401176
serological survey of virus infection among wild house mice (mus domesticus) in the uk.the serological prevalence of 13 murine viruses was surveyed among 103 wild-caught and 51 captive-bred house mice (mus domesticus), originating from several trapping locations in northwest england, using blood samples obtained during routine health screening of an established wild mouse colony. a high proportion of recently caught wild mice were seropositive for mouse hepatitis virus (86%), mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%), mouse parvovirus (59%) and ...200717430622
spontaneous exocrine pancreas hypoplasia in specific pathogen-free c3heb/fej and 101/h mouse pups causes steatorrhea and runting.under specific pathogen-free conditions, 1.3% to 1.8% of litters born in our inbred 101/h and c3heb/fej mouse colonies had pups with steatorrhea and runting. clinically affected male and female pups were first identified when they were from 14 to 25 d old. unaffected littermates were healthy and were weaned successfully. postmortem findings in 8 clinically affected mice included a small, poorly differentiated exocrine pancreas comprising cytokeratin-negative duct-like structures but lacking reco ...200717536623
evidence for virus closely related to avian myeloblastosis-associated virus type 1 in a commercial stock of chickens.a two-round nested polymerase chain reaction assay detected rous associated virus-1 (rav-1), a prototype laboratory strain of avian leukosis virus of subgroup a (alv-a). surprisingly, the test failed to detect three field isolates of alv-a but did detect virus in one commercial stock of chickens (stock f). the sequence analysis of a core of 290 nucleotides of the env gene gave evidence that the virus from stock f was closely related to avian myeloblastosis-associated virus type one (mav-1). othe ...200317585462
mouse adenovirus type 1 infection of natural killer cell-deficient mice.natural killer (nk) cells contribute to the initial nonspecific response to viral infection, and viruses exhibit a range of sensitivities to nk cells in vivo. we investigated the role of nk cells in infection of mice by mouse adenovirus type 1 (mav-1) using antibody-mediated depletion and knockout mice. mav-1 causes encephalomyelitis and replicates to highest levels in brains. nk cell-depleted mice infected with mav-1 showed brain viral loads 8-20 days p.i. that were similar to wild-type control ...200818155121
card6 is interferon inducible but not involved in nucleotide-binding oligomerization domain protein signaling leading to nf-kappab activation.we have previously reported the cloning and characterization of card6, a caspase recruitment domain (card)-containing protein that is structurally related to the interferon (ifn)-inducible gtpases. card6 associates with microtubules and with receptor-interacting protein 2 (rip2). rip2 mediates nf-kappab activation induced by the intracellular nucleotide-binding oligomerization domain (nod) receptors that sense bacterial peptidoglycan. here we report that the expression of card6 and rip2 in bone ...200818160713
exacerbation of established pulmonary fibrosis in a murine model by gammaherpesvirus.idiopathic pulmonary fibrosis is a progressive disease with high mortality. although most patients have a slow, progressive course, some patients will have an acute deterioration in function or acute exacerbation, which carries a poor prognosis. in some cases, acute deterioration is associated with infection. herpesviruses have been associated with this disease. fibrocytes have also been shown to be important in the pathogenesis of pulmonary fibrosis.200818187693
adenovirus il-13-induced airway disease in mice: a corticosteroid-resistant model of severe asthma.interleukin 13 (il-13) is considered to be a key driver of the development of airway allergic inflammation and remodeling leading to airway hyperresponsiveness (ahr). how precisely il-13 leads to the development of airway inflammation, ahr, and mucus production is not fully understood. in order to identify key mediators downstream of il-13, we administered adenovirus il-13 to specifically induce il-13-dependent inflammation in the lungs of mice. this approach was shown to induce cardinal feature ...200818258919
recovery of humoral immunity is critical for successful antiviral therapy in disseminated mouse adenovirus type 1 infection.severe adenovirus infections in transplant recipients undergoing immunosuppressive therapy are of increasing concern. controversy exists on the contribution of antiviral therapy and the host immune response to recovery from these infections. here, we established a systemic mouse adenovirus type 1 (mav-1) infection in cyclophosphamide (cyp)-treated balb/c mice. cyp was administered at 100 mg per kg of body weight every other day for 2, 3, or 4 weeks, thereby inducing general but reversible leukop ...200818268085
upgrading mouse health and welfare: direct benefits of a large-scale rederivation programme.we report the outcome of a 30-month programme to rederive 310 specific pathogen-free mouse strains to populate a new individually ventilated cage barrier facility at the mary lyon centre (mlc), medical research council (mrc) harwell. the mice were rederived in a self-contained quarantine suite and embryo-recipient females were health-screened to assess microbiological status, before moving their offspring into the new facility. the mlc currently houses approximately 49,000 mice in about 9750 cag ...200818435871
gammaherpesvirus modulation of mouse adenovirus type 1 pathogenesis.immune function is likely to be shaped by multiple infections over time. infection with one pathogen can confer cross-protection against heterologous pathogens. we tested the hypothesis that latent murine gammaherpesvirus 68 (gammahv68) infection modulates host inflammatory responses and susceptibility to mouse adenovirus type 1 (mav-1). mice were infected intranasally (i.n.) with gammahv68. 21 days later, they were infected i.n. with mav-1. we assessed cytokine and chemokine expression by quant ...200818768196
mouse adenovirus type 1 and human adenovirus type 5 differ in endothelial cell tropism and liver targeting.for adenovirus vectors derived from human serotype 5 (ad5), the efficiency and safety after intravascular delivery is hindered by their sequestration in nontarget tissues, predominantly the liver. the latter is largely dictated by adenovirus binding to blood coagulation zymogens. in addition, several target cells, such as endothelial and smooth muscle cells, are difficult to transduce by ad5 due to the low expression of the primary coxsackie-adenovirus receptor (car). therefore, alternative aden ...200919065608
usage of integrin and heparan sulfate as receptors for mouse adenovirus type 1.adenovirus fiber knobs are the capsid components that interact with binding receptors on cells, while an arg-gly-asp (rgd) sequence usually found in the penton base protein is important for the interaction of most adenoviruses with integrin entry receptors. mouse adenovirus type 1 (mav-1) lacks an rgd sequence in the virion penton base protein. we tested whether an rgd sequence found in the mav-1 fiber knob plays a role in infection. treatment of cells with a competitor rgd peptide or a purified ...200919176624
novel immunocompetent murine tumor model for evaluation of conditionally replication-competent (oncolytic) murine adenoviral vectors.oncolytic adenoviral vectors that express immunostimulatory transgenes are currently being evaluated in clinic. preclinical testing of these vectors has thus far been limited to immunodeficient xenograft tumor models since human adenoviruses do not replicate effectively in murine tumor cells. the effect of the immunostimulatory transgene on overall virus potency can therefore not be readily assessed in these models. here, a model is described that allows the effective testing of mouse armed onco ...200919193803
a novel cardiotropic murine adenovirus representing a distinct species of mastadenoviruses.during cell culture isolation experiments to recover dobrava hantavirus from a suspension of liver from a striped field mouse (apodemus agrarius), an unknown virus was coisolated. atypically for hantaviruses, it had extensive cytopathic effects. using a random pcr approach, it was identified as a novel murine adenovirus, madv-3 (for madv type 3). a plaque-purified virus clone was prepared and further characterized. the complete genome sequence of madv-3 was determined to be 30,570 bp in length. ...200919297486
adeno-associated virus infection of murine fibroblasts with help provided by mouse adenovirus.adeno-associated virus (aav-2) replicates to high titers when host cells are coinfected with a helper virus. here we analyzed the coinfection of aav-2 and mouse adenovirus (mav-1) in murine fibroblasts. we observed that aav-2/mav-1 coinfected nih 3t3 cells produced approximately 10-40-fold less aav-2 dnase resistant particles than hela cells. levels of aav-2 dna replication were approximately 30-fold less in 3t3 cells as compared to hela cells coinfected with human adenovirus (ad-5). a study of ...200919464040
mouse adenovirus type 1 infection of macrophages.mouse adenovirus type 1 (mav-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. mav-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus. here we determined the extent and functional importance of macrophage infection by mav-1. bone marrow-derived macrophages expressed mav-1 mrnas and proteins upon ex vivo infection. adherent peritonea ...200919540545
effects of allergic airway disease on mouse adenovirus type 1 respiratory infection.virus infection may contribute to asthma pathogenesis. in turn, a th2-polarized pulmonary environment may increase host susceptibility to infection. we used a cockroach antigen (cra) model of allergic airway disease to test the hypothesis that th2 cytokine overproduction increases susceptibility to mouse adenovirus type 1 (mav-1). cra sensitization led to upregulated lung expression of il-4 and il-13, lung cellular inflammation, and exaggerated airway mucus production. following intranasal mav-1 ...200919564030
mouse adenovirus type 1-induced breakdown of the blood-brain barrier.infection with mouse adenovirus type 1 (mav-1) results in fatal acute encephalomyelitis in susceptible mouse strains via infection of brain endothelial cells. wild-type (wt) mav-1 causes less brain inflammation than an early region 3 (e3) null virus in c57bl/6 mice. a mouse brain microvascular endothelial cell line infected with wt mav-1 had higher expression of mrnas for the proinflammatory chemokines ccl2 and ccl5 than mock- and e3 null virus-infected cells. primary mouse brain endothelial cel ...200919570856
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
helicobacter spp. in wild mice (peromyscus leucopus) found in laboratory animal facilities.wild rodents are a potential source for pathogen introduction into laboratory animal research facilities. a study was designed to assess wild mice found at our institution by infectious disease surveillance. wild white-footed mice (peromyscus leucopus) were captured with live capture traps placed in areas in which wild mice had been reported in several animal facilities. captured animals were euthanized by inhalation of co(2), blood was collected by cardiocentesis (n = 10), and necropsy was perf ...200919930823
the major locus for mouse adenovirus susceptibility maps to genes of the hematopoietic cell surface-expressed ly6 family.susceptibility to mouse adenovirus type 1 is associated with the major quantitative trait locus msq1. msq1 was originally mapped to a 13-mb region of mouse chromosome (chr) 15 in crosses between sjl/j and balb/cj inbred mice. we have now narrowed msq1 to a 0.75-mb interval from 74.68 to 75.43 mb, defined by two anonymous markers, rs8259436 and d15spn14, using data from 1396 backcross mice. the critical interval includes 14 ly6 or ly6-related genes, including ly6a (encoding sca-1/tap), ly6e (sca- ...201020164425
forensic investigation of a 1986 outbreak of osteopetrosis in commercial brown layers reveals a novel avian leukosis virus-related genome.avian leukosis virus (alv) is known to cause several neoplastic conditions in chickens, such as b-cell lymphomas, myelocytomas, erythroblastosis, and other types of neoplasia including osteopetrosis. we describe herein the identification of unique alv-related proviral dna sequences in an archived chicken bone affected with osteopetrosis. the osteopetrotic bone was obtained from an affected 46-week-old brown layer during an outbreak of osteopetrosis in costa rica in 1986. analysis of proviral dna ...201020945777
assessment of the efficacy of the first water system for emergency hospital use.the first water responder b package water treatment device was evaluated for its ability to reduce the levels of spiked indicators and pathogens (escherichia coli, ms2 coliphage, murine adenovirus, and cryptosporidium oocysts) in a surface water to partially evaluate its appropriateness to be used to provide safe drinking water to hospitals during emergency situations.201121402824
limited effects of muc1 deficiency on mouse adenovirus type 1 respiratory infection.muc1 (muc1 in humans) is a membrane-tethered mucin that exerts anti-inflammatory effects in the lung during bacterial infection. muc1 and other mucins are also likely to form a protective barrier in the lung. we used mouse adenovirus type 1 (mav-1, also known as madv-1) to determine the role of muc1 in the pathogenesis of an adenovirus in its natural host. following intranasal inoculation of wild type mice, we detected increased tnf-╬▒, a cytokine linked to muc1 production, but no consistent cha ...201121816184
Genomic and phylogenetic analyses of murine adenovirus 2.Murine adenoviruses (MAdV) are supposedly the oldest members of the genus Mastadenovirus. Currently, there are three distinct MAdV types known with rather different tropism and pathology. Here we report and annotate the DNA sequence of the full genome of MAdV-2. It was found to consist of 35,203bp thus being considerably larger than the genomes of the other two MAdV types. The increased size of the MAdV-2 genome is generally due to larger genes and ORFs, although some differences in the number o ...201121683742
polymorphisms in ly6 genes in msq1 encoding susceptibility to mouse adenovirus type 1.strain-specific differences in susceptibility to mouse adenovirus type 1 (mav-1) are linked to the quantitative trait locus msq1 on mouse chromosome 15. this region contains 14 ly6 or ly6-related genes, many of which are known to be expressed on the surface of immune cells, suggesting a possible role in host defense. we analyzed these genes for polymorphisms between mav-1-susceptible and mav-1-resistant inbred mouse strains. sequencing of cdnas identified 12 coding-region polymorphisms in 201010 ...201122101863
contribution of a single host genetic locus to mouse adenovirus type 1 infection and encephalitis.susceptibility to mouse adenovirus type 1 (mav-1) is mouse strain dependent; susceptible mice die from hemorrhagic encephalomyelitis. the mav-1 susceptibility quantitative trait locus msq1 accounts for ~40% of the phenotypic (brain viral load) variance that occurs between resistant balb/c and susceptible sjl mice after mav-1 infection. using an interval-specific congenic mouse strain (c.sjl-msq1(sjl)), in which the sjl-derived allele msq1(sjl) is present in a balb/c background, we demonstrate th ...201222647790
assessing the feasibility of fly based surveillance of wildlife infectious diseases.monitoring wildlife infectious agents requires acquiring samples suitable for analyses, which is often logistically demanding. a possible alternative to invasive or non-invasive sampling of wild-living vertebrates is the use of vertebrate material contained in invertebrates feeding on them, their feces, or their remains. carrion flies have been shown to contain vertebrate dna; here we investigate whether they might also be suitable for wildlife pathogen detection. we collected 498 flies in taï n ...201627901062
matrix metalloproteinase activity in infections by an encephalitic virus, mouse adenovirus type 1.mouse adenovirus type 1 (mav-1) infection causes encephalitis in susceptible strains of mice and alters the permeability of infected brains to small molecules, which indicates disruption of the blood-brain barrier (bbb). under pathological conditions, matrix metalloproteinases (mmps) can disrupt the bbb through their proteolytic activity on basement membrane and tight junction proteins. we examined whether mav-1 infection alters mmp activity in vivo and in vitro infected mav-1-susceptible sjl mi ...201728053109
a protective role for interleukin-1 signaling during mouse adenovirus type 1-induced encephalitis.interleukin-1β (il-1β), an inflammatory cytokine and il-1 receptor ligand, has diverse activities in the brain. we examined whether il-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (mav-1) infection, using mice lacking the il-1 receptor (il1r1(-/-) mice). il1r1(-/-) mice demonstrated reduced survival, greater disruption of the blood-brain barrier (bbb), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control c57bl/6j mi ...201727903802
interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection.the immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. the immunoproteasome also influences immune function by enhancing peptide presentation by mhc class i and promotes inflammation via iκb degradation and activation of nf-κb. we used mouse adenovirus type 1 (mav-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly incr ...201627560373
mouse adenovirus type 1 early region 1a effects on the blood-brain barrier.mouse adenovirus type 1 (mav-1) infects endothelial cells and disrupts the blood-brain barrier (bbb), causing encephalitis in inbred and outbred mice. using a virus mutant that does not produce the early region 1a protein e1a, we investigated whether the activity of this known viral transcriptional regulator is needed for bbb disruption and other phenotypes associated with encephalitis. the wild-type (wt) virus and e1a mutant virus caused similar levels of permeability of sodium fluorescein in b ...201727303733
defensins potentiate a neutralizing antibody response to enteric viral infection.α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. using a mouse model deficient in activated α-defensins in the small intestine, we show that paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (madv-1). survival d ...201626933888
prostaglandin e2 production during neonatal respiratory infection with mouse adenovirus type 1.neonatal mice are more susceptible than adults to mouse adenovirus type 1 (mav1) respiratory infection. in adult mice, mav-1 respiratory infection induces production of prostaglandin e2 (pge2), a lipid mediator that exerts suppressive effects on a variety of host immune functions. we tested the hypothesis that exaggerated pge2 production in neonatal mice contributes to increased susceptibility to mav-1. pge2 concentrations were lower in lungs of uninfected neonatal mice than in adults. pge2 prod ...201626795547
prostaglandin e2 production and t cell function in mouse adenovirus type 1 infection following allogeneic bone marrow transplantation.adenovirus infections are important complications of bone marrow transplantation (bmt). we demonstrate delayed clearance of mouse adenovirus type 1 (mav-1) from lungs of mice following allogeneic bmt. virus-induced prostaglandin e2 (pge2) production was greater in bmt mice than in untransplanted controls, but bmt using pge2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the pge2 analog misoprostol did not affect virus clearance. lympho ...201526407316
proinflammatory effects of interferon gamma in mouse adenovirus 1 myocarditis.adenoviruses are frequent causes of pediatric myocarditis. little is known about the pathogenesis of adenovirus myocarditis, and the species specificity of human adenoviruses has limited the development of animal models, which is a significant barrier to strategies for prevention or treatment. we have developed a mouse model of myocarditis following mouse adenovirus 1 (mav-1) infection to study the pathogenic mechanisms of this important cause of pediatric myocarditis. following intranasal infec ...201525320326
il-17 contributes to neutrophil recruitment but not to control of viral replication during acute mouse adenovirus type 1 respiratory infection.il-17-producing cd4(+) helper t cells (th17 cells) promote inflammatory responses to many pathogens. we used mouse adenovirus type 1 (mav-1) to determine contributions of il-17 to adenovirus pathogenesis. mav-1 infection of c57bl/6 mice upregulated lung expression of il-17 and the th17-associated factors il-23 and rorγt. only cd4(+)t cells were associated with virus-specific il-17 production. fewer neutrophils were recruited to airways of il-17(-/-) mice following mav-1 infection, but there were ...201424889245
prostaglandin e2 induction during mouse adenovirus type 1 respiratory infection regulates inflammatory mediator generation but does not affect viral pathogenesis.respiratory viruses cause substantial disease and are a significant healthcare burden. virus-induced inflammation can be detrimental to the host, causing symptoms during acute infection and leading to damage that contributes to long-term residual lung disease. prostaglandin e2 (pge2) is a lipid mediator that is increased in response to many viral infections, and inhibition of pge2 production during respiratory viral infection often leads to a decreased inflammatory response. we tested the hypoth ...201324147040
intracellular antibody receptor trim21 prevents fatal viral infection.host species have evolved mechanisms that can inhibit pathogen replication even after a cell has been successfully invaded. here we show that tripartite-motif protein 21 (trim21), a ubiquitously expressed e3 ubiquitin ligase that targets viruses inside the cytosol, protects mice against fatal viral infection. upon infection with mouse adenovirus-1, naive mice lacking trim21 succumb to encephalomyelitis within 7 d. in contrast, wild-type mice rapidly up-regulate trim21 and control viremia. trim21 ...201323840060
simultaneous neutralization and innate immune detection of a replicating virus by trim21.tripartite motif-containing 21 (trim21) is a cytosolic immunoglobulin receptor that mediates antibody-dependent intracellular neutralization (adin). here we show that trim21 potently inhibits the spreading infection of a replicating cytopathic virus and activates innate immunity. we used a quantitative pcr (qpcr)-based assay to measure in vitro replication of mouse adenovirus type 1 (mav-1), a virus that causes dose-dependent hemorrhagic encephalitis in mice. using this assay, we show that genet ...201323596308
interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.application of human adenovirus type 5 (ad5) derived vectors for cancer gene therapy has been limited by the poor cell surface expression, on some tumor cell types, of the primary ad5 receptor, the coxsackie-adenovirus-receptor (car), as well as the accumulation of ad5 in the liver following interaction with blood coagulation factor x (fx) and subsequent tethering of the fx-ad5 complex to heparan sulfate proteoglycan (hspg) on liver cells. as an alternative vector, mouse adenovirus type 1 (mav-1 ...201222347482
susceptibility to acute mouse adenovirus type 1 respiratory infection and establishment of protective immunity in neonatal mice.there is an incomplete understanding of the differences between neonatal immune responses that contribute to the increased susceptibility of neonates to some viral infections. we tested the hypothesis that neonates are more susceptible than adults to mouse adenovirus type 1 (mav-1) respiratory infection and are impaired in the ability to generate a protective immune response against a second infection. following intranasal infection, lung viral loads were greater in neonates than in adults durin ...201222345470
recombination of the epsilon determinant and corneal tropism: human adenovirus species d types 15, 29, 56, and 69.viruses within human adenovirus species d (hadv-d) infect epithelia at essentially every mucosal site. hypervariable loops 1 and 2 of the hexon capsid protein contain epitopes that together form the epsilon determinant for serum neutralization. we report our analyses comparing hadv-d15, 29, 56, and the recently identified type 69, each with highly similar hexons and the same serum neutralization profile, but otherwise disparate genomes. of these, only hadv-d type 56 is associated with epidemic k ...201526343864
generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease.the emergence of middle east respiratory syndrome-coronavirus (mers-cov) in the middle east since 2012 has caused more than 900 human infections with ∼40% mortality to date. animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against mers-cov infection. nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. although a mouse lung infection model has been described using adenovirus vectors expressing h ...201525589660
ultrastructure of adenovirus keratitis.we determined the ultrastructure of mouse adenovirus keratitis, a model for human adenovirus keratitis.201525564451
efficacy of direct detection of pathogens in naturally infected mice by using a high-density pcr array.we used a high-density array of real-time pcr assays for commonly reported rodent infectious agents (pria) to test naturally infected index mice and sentinel mice exposed by contact and soiled-bedding transfer. pria detected 14 pathogens--including viruses, bacteria, fur mites, pinworms, and enteric protozoa--in 97.2% of 28 pooled fecal samples, fur-perianal swabs, and oral swabs from 4 cages containing a total of 10 index mice. among these pathogens, pria (like conventional health monitoring me ...201324351765
natural infection and transmission of a retrovirus closely related to myeloblastosis-associated virus type 1 in egg-type chickens.myeloblastosis-associated virus type 1 (mav-1) is an exogenous avian retrovirus with oncogenic potential. mav-1 was detected in young chicks hatching from eggs produced by an experimental genetic line of egg-type chickens. transmissibility of mav-1 had not been documented previously. this investigation was intended to partially characterize the virus involved and to study its transmissibility and oncogenicity in naturally and contact-infected chickens. commercially produced white and brown layer ...201222545523
small-size recombinant adenoviral hexon protein fragments for the production of virus-type specific antibodies.adenoviruses are common pathogens infecting animals and humans. they are classified based on serology, or genome sequence information. these methods have limitations due to lengthy procedures or lack of infectivity data. adenoviruses are easy to produce and amenable to genetic and biochemical modifications, which makes them a powerful tool for biological studies, and clinical gene-delivery and vaccine applications. antibodies directed against adenoviral proteins are important diagnostic tools fo ...201728821267
contributions of cd8 t cells to the pathogenesis of mouse adenovirus type 1 respiratory infection.cd8 t cells are key components of the immune response to viruses, but their roles in the pathogenesis of adenovirus respiratory infection have not been characterized. we used mouse adenovirus type 1 (mav-1) to define cd8 t cell contributions to the pathogenesis of adenovirus respiratory infection. cd8 t cell deficiency in β2m(-/-) mice had no effect on peak viral replication in lungs, but clearance of virus was delayed in β2m(-/-) mice. virus-induced weight loss and increases in bronchoalveolar ...201728410483
alpha-defensin-dependent enhancement of enteric viral infection.the small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. although they most commonly function as potent antivirals in cell culture, enteric α-defensins have also been shown to enhance some viral infections in vitro. efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. to address this issue, here we use primary stem cell-derived small intestinal ...201728622386
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
opportunistic sampling of wild native and invasive birds reveals a rich diversity of adenoviruses in australia.little is known about the diversity of adenoviruses in wild birds and how they have evolved and are maintained in complex ecosystems. in this study, 409 samples were collected from woodland birds caught for banding (droppings), birds submitted to a wildlife hospital (droppings and tissues), silver gulls (droppings or tissues), and feral pigeons (columbia livia; oral, cloacal swabs, or tissues) from the greater sydney area in nsw, australia. additional samples were from native pigeons and doves ( ...202032411389
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