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[Appearance of multinucleated giant cells in association with an adenovirus infection in two guinea pigs].

In two guinea pigs (five years old, neutered male, and two and a half months old male, respectively) suffering from interstitial pneumonia, multinucleated giant cells were observed histologically in lungs, spleen and liver. The giant cells showed intranuclear, pale basophilic inclusions. Adenovirus could be demonstrated by electron microscopy.The multinucleated cells are supposed to be of histiocytic origin, since they contained variable amounts of haemosiderin in their cytoplasm. Formation of histiocyte-derived syncytia as a result of virus-induced cell fusion is discussed.

Adenoviridae Infections↗

Fatal adenovirus infection associated with new genome type.

The first fatal case caused by the new genome type 7i is described in an 8-month-old boy requiring long-term respiratory support who developed Reye's syndrome, acute respiratory distress, and bronchiolitis obliterans with fatal evolution. Adenovirus was detected in nasopharyngeal secretions and was persistently positive during hospitalization. IgM and IgG adenovirus antibody titers measured in serum by enzyme-linked immunoassay (EIA) were 1:32 and 1:800, respectively. Serum interleukins (IL) and interferons (IFN) measured by EIA were as follows: IL-2, 110 pg/ml; IL-6, 300 pg/ml; IL-8, 7,000 pg/ml; TNF-alpha, 35 pg/ml, IL-1 and IL-4 undetectable, IFN-alpha 2,200 pg/ml, and IFN-gamma 700 pg/ml. Virologic studies showed that adenovirus isolated belonged to subgenus B, and digestion of viral DNA with Bam HI, Sma I, Bgl II, and Hind III identified the isolate as belonging to genome type 7i. Autopsy showed bronchiolitis obliterans with diffuse alveolar damage and perivenular fatty degeneration with polymorphonuclear infiltrates in the periportal spaces. The difficulty in obtaining adequate oxygenation with minimization of iatrogenic oxygen injury is discussed.

Adenoviridae↗

Fatal pulmonary edema in white-tailed deer (Odocoileus virginianus) associated with adenovirus infection.

Sporadic sudden deaths in adult white-tailed deer occurred from November 1997 through August 1998 on an Iowa game farm. Three of the 4 deer necropsied had severe pulmonary edema, widespread mild lymphocytic vasculitis, and amphophilic intranuclear inclusion bodies in scattered endothelial cells in blood vessels in the lung and abdominal viscera. Immunohistochemistry with bovine adenovirus 5 antisera and transmission electron microscopy demonstrated adenoviral antigen and nucleocapsids, respectively, within endothelial cells. Adenovirus was isolated in cell culture from 1 of the affected deer. The isolate was neutralized by California black-tailed deer adenovirus antiserum. These findings indicate that adenovirus should be considered in the differential diagnosis of both black-tailed and white-tailed deer with pulmonary edema and/or hemorrhagic enteropathy.

Adenoviridae↗

[Virological diagnosis of ocular adenovirus infection].

For laboratory diagnosis, virus isolation and identification from conjunctival swabs should be combined with serology (two blood specimens: early and 14 days or later after onset of disease). The group-specific complement fixation fails in almost one-half of the cases. Additional type-specific reactions (neutralization, hemagglutination inhibition, type-specific complement fixation) may be performed with adenovirus 8 and, in epidemic outbreaks, also with other types. Immunofluorescence procedures have proved to be of limited value; rapid diagnostic procedures are not yet available.

Adenoviridae Infections↗

Adenovirus infection in two calves.

Two 2-week-old calves with pyrexia, diarrhea, and subsequent dehydration were treated symptomatically for 1 week, but without favorable response. At necropsy, foci of necrosis were found in the abomasum and rumen of each calf. The small and large intestineswere dilated by grayish, turbid fluid. Numerous large amphophilic, intranuclear inclusions in endothelial cells of blood vessels in the abomasum and rumen, in endothelial cellsof the adrenal cortical sinusoids and renal glomeruli, and in intestinal epithelial cells were identified as adenovirus particles.

Abomasum↗

[Epidemic keratoconjunctivitis. Laboratory study of patients infected with adenovirus type 8].

The authors tried to detect, using different methods, the causal agent of the disease in eight patients with epidemic keratoconjunctivitis. From the conjunctival sacs of one ambulatory patient and six of seven patients hospitalized on account of other eye diseases they isolated 11 strains of adenovirus type 8 on cell cultures from human embryonic lungs. Using direct and indirect ELISA, they detected adenovirus antigen in four of seven examined smears from the conjunctival sac without previous cultivation. In smears from the nasopharynx they did not detect adenoviruses by either of the two methods. Antibodies were assessed by micromodifications of the virus neutralizing test, by the complement fixation reaction and ELISA. A significant rise of antibodies against adenovirus type 8 and adenovirus hexone resp. was found in different six of eight examined pairs of sera. The combination of these three serological methods made it possible to confirm adenovirus infection in all eight patients.

Adenoviridae Infections↗

Neurons in Golgi-stain-like images revealed by GFP-adenovirus infection in vivo.

Neurons in the adult brain have a very complex morphology with many processes, including tremendously long axons. Since dendrites and axons play key roles in the input and output of neural information, respectively, the visualization of complete images of these processes is necessary to reveal the mechanism of neural information processing. Here we made a recombinant adenovirus vector which encodes green fluorescent protein (GFP) tagged with a palmitoylation site, a membrane-targeting signal, produced specific antibodies to GFP, and used them as probes for staining the nervous system. In the neocortex, after injection of the recombinant virus and immunoperoxidase staining with the antibodies, many different types of cells were labeled in a Golgi stain-like fashion. Although the number of labeled cells varied depending on the amount of virus injected, the recombinant virus was considered to be infectious to cortical neurons of all cell types without selectivity. In contrast, the viral infection in the cerebellar cortex and superior cervical ganglion showed some selectivity toward the cell type. It is expected that this recombinant virus will be a useful tool for the morphological analysis of neuronal connections, especially the analysis of microcircuitry in the cerebral cortex.

Adenoviridae↗

Multisystemic adenovirus infection in broiler chicks with hypoglycemia and spiking mortality.

The search for a solitary cause of spiking mortality (so-called spiking mortality syndrome [SMS]) among broiler chicks has been thwarted by the fact that many agents will cause similar mortality histograms. Recently, severe hypoglycemia has been said to be a characteristic finding in chicks that die with SMS. In the present case study, we report adenovirus inclusions in the pancreas, small intestines, and liver of chicks with hypoglycemia and spiking mortality. We attributed the hypoglycemia and mortality to hepatic insufficiency.

Adenoviridae Infections↗

Enhanced adenovirus infection of melanoma cells by fiber-modification: incorporation of RGD peptide or Ad5/3 chimerism.

The incidence of malignant melanoma has been increasing. Unfortunately, advanced melanomas are rarely curable with standard therapy; therefore, new forms of treatment such as gene therapy are needed. The success of gene delivery or oncolysis depends on the nature of the vector. Adenoviral vectors are advantageous for several reasons; however, they are dependent on CAR (coxsackie and adenovirus receptor) which is deficient or heterogeneously expressed on melanoma cells in situ. Correspondingly, transduction of freshly purified melanoma cells has been shown to be minimal or variable. In order to overcome this shortcoming, it is necessary to construct tropism modified adenoviral vectors. With this goal in mind, we generated two tropism modified vectors, Ad5lucRGD which has an RGD motif incorporated into the HI loop of the fiber knob and Ad5/3luc1 which contains the tail and shaft domain of the Ad5 fiber and the knob domain of the Ad3 fiber. Herein we demonstrate that Ad5/3luc1 infects CAR-negative primary melanoma cells 1128 times better than Ad5luc1 and 34 times better than Ad5lucRGD. Furthermore we show that Ad5/3luc1 and Ad5lucRGD infect via a CAR independent route by blocking the CAR receptor. In addition, we show that the infectivity of the cells correlates with the expression of CAR and Ad3 receptors determined by FACS analysis. Therefore, Ad5/3 is very attractive as a potential therapeutic vector for malignant melanoma.

Adenoviruses, Human↗

Coxsackievirus and adenovirus infection. Association with acute febrile and juvenile rheumatoid arthritis.

The prearthritic manifestations of juvenile rheumatoid arthritis in a 16-year-old boy were associated with a rise in coxsackievirus B3 and A9 neutralizing antibody titers from 1:16 to larger than or equal to 1:512, and 1:64 to 1:512, respectively. Recurrent polyarthritis followed and has persisted for three years. Adenovirus 7 was isolated from the pericardial fluid of a 9-year-old girl in whom juvenile rheumatoid arthritis then developed. Of 11 patients with acute, nonspecific, febrile arthritis subsequently studied, fourfold or greater antibody elevations occurred against coxsackieviruses in five, and against rubella and varicella-zoster virus in two. Antibody titers against other viral (and Mycoplasma) antigens remained stable. These findings suggest that coxsackieviruses, as well as other common viruses, may cause acute, nonspecific, febrile arthritis. In certain instances, such infection may be related to the development of juvenile rheumatoid arthritis.

Acute Disease↗

Falcon adenovirus infection in breeding Taita falcons (Falco fasciinucha).

Four female and 3 male Taita falcons (Falco fasciinucha) out of a breeding colony of 14 Taita falcons (7 pairs) died during the breeding season after showing lethargy and anorexia for 1 to 2 days. All animals were submitted for necropsy. Gross lesions in the female falcons were characterized by anemia secondary to marked hemorrhage into the ovary and oviduct, serofibrinous effusion into the cardioabdominal cavity and serosal petechiae. In addition, marked necrotizing splenitis and pulmonary hemorrhage were present. Histologically, the female falcons had mild necrotizing hepatitis with numerous intranuclear inclusion bodies and necrotizing splenitis with rare inclusion bodies. There were no gross lesions in the male falcons, and the histological lesions were characterized by urate deposition and rare intranuclear inclusion bodies in the renal tubular epithelial cells. Adenoviral particles were found by electron microscopy in the cloacal contents of the female Taita falcons but not in the male falcons. DNA in situ hybridization revealed widespread aviadenoviral nucleic acid within the nuclei of hepatocytes, renal tubular epithelial cells, and adrenal cells in the female falcons but no aviadenoviral nucleic acid in 1 male falcon and only a low quantity of adenoviral nucleic acid in the liver and kidney of another male Taita falcon. PCR amplified aviadenoviral DNA in the liver and intestine of all Taita falcons. The amplicons were sequenced, and the virus was identified as falcon adenovirus. The deaths of the female and male birds were attributed to the aviadenovirus infection.

Adenoviridae Infections↗

Detection of microorganisms in the tracheal aspirates of preterm infants by polymerase chain reaction: association of adenovirus infection with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is recognized as an important cause of morbidity and mortality in preterm infants. Because the role of congenital infections in BPD has been debated, the purpose of this study was to test the hypothesis that detection of infectious agents in tracheal aspirate samples was associated with the development of BPD. Tracheal aspirate samples were obtained within the 1st week of life and screened by polymerase chain reaction for adenovirus, cytomegalovirus, parvovirus, enteroviruses, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma pneumoniae, and Chlamydia species. BPD was defined as persistent oxygen dependence at 28 d of age and 36 wk postconceptional age (PCA). Infants that expired before these time points were excluded from statistical analysis. Out of 89 infants studied, at 28 d of life, 13 had expired, 45 had BPD, and 31 had no BPD (controls). At 36 wk PCA, 15 infants expired, 39 still had BPD, and 35 did not. A significant increase in the frequency of adenovirus genome was identified in BPD patients compared with controls, both at 28 d of life (12/45 = 27% versus 1/31 = 3%: p< or =0.01) and at 36 wk PCA (10/39 = 29% versus 2/35 = 6%: p = 0.01). Other microorganisms were rarely detected and not associated with the development of BPD. This is the first study reporting the frequency of detection of adenovirus DNA in tracheal aspirate samples obtained during the 1st week of life from infants with BPD and suggests that prenatal acquisition may be important in the development of BPD.

Adenoviridae↗

The transcriptional role of host DNA-dependent RNA polymerases in adenovirus-infected KB cells.

From the present experiments, we can conclude that late in infection two classes of DNA-dependent RNA polymerase transcribe the viral genome. Although we cannot definitively exclude the possibility that one or both of these enzymes are coded for by the virus, it appears more probable that these are hos enzymes, because of the coincidence of the alpha-amanitin sensitivities for synthesis of specific viral RNAs with the toxin sensitivities of the respective host RNA polymerases. Furthermore, the chromatographic properties of the enzymes, the alpha-amanitin sensitivities of the purified RNA polymerases and the levels of solubilized activities are the same for uninfected and late infected cells. It seems probable that some virus-coded or virus-induced factor(s) modifies either the selectivity or the activity of these host RNA polymerases. As an example, the "inactivation" of RNA polymerase I activity in vivo or the increased endogenous activity of isolated infected cell nuclei, without changes in the solubilized level of the respective RNA polymerases, could be mediated by such factor(s). The effect of such factors may not be detected by activity measurements on exogenous DNA, because it acts as a nonspecific template. Analysis of such factors will require reconstitution of appropriate in vitro systems, which retain some transcriptional specificity. Since several viral mRNAs synthesized at late times (Tal et al. 1974) and the 5.5S RNA (J. Pan, pers, comm.) are transcribed from the same region (R-R1 restriction enzyme fragment A), initiation and termination signals for both RNA polymerase II and III are contained in this portion of the genome. Further studies of the interaction of these two enzymes with the adenovirus 2 genome should contribute to understanding the control of transcription in eukaryotic cells, in particular in the case of virus-infected or -transformed cells.

Adenoviridae↗

An adenovirus infection of the kidney of Franklin's ground squirrels (Spermophilus franklini) in Saskatchewan, Canada.

During routine pathological studies of Franklin's ground squirrels (Spermophilus franklini) collected during a predator control program, basophilic intranuclear inclusions were found in the collecting tubule epithelium of the renal papillae in seven of 13 squirrels. This was associated with marked karyomegaly in affected cells. An inflammatory response was not seen in the adjacent tissues. Electron microscopic examination of affected cells demonstrated that the enlarged nuclei contained numerous virus-like particles. Autoculture and serial passage of renal medullary cells resulted in the isolation of virus particles producing intranuclear inclusions and cytopathic effect. The virus possessed properties typical of adenoviruses, but showed no evidence of hemagglutinating activity with a range of species of erythrocytes tested under several temperature conditions. The isolates were relatively host-cell specific; they failed to grow in hamster and rabbit kidney cell lines and in ground squirrel kidney cortical cells.

Adenoviridae Infections↗