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PubMed2000

Evaluation of the efficacy of 2',3'-dideoxycytidine against adenovirus infection in a mouse pneumonia model.

The antiviral activity of 2',3'-dideoxycytidine (ddC) has been investigated in a mouse pneumonia model. Consolidation of lung, histopathological changes, DNA synthesis as well as levels of TNFalpha were assayed. In this in vivo model, the oral administration of ddC twice daily over 4 days, displayed an inhibitory effect. The drug significantly reduced histopathologic responses. Analysis indicated that under treatment pulmonary lesions were less severe than those of untreated controls. These data confirm the in vitro activity of ddC against adenovirus. Thus, ddC represents a potential therapeutic approach for inhibiting adenovirus infection and may offer promise as an anti-adenovirus agent for immunocompromised patients in whom serious adenovirus infection may prove fatal.

Adenoviridae Infections↗

PubMed1977

Severe disseminated adenovirus infection successfully treated with a thymic humoral factor, THF.

Adenovirus and other usually benign viral infections may occasionally be associated with severe fulminant disease, often accompanied by acute acquired cellular immunodeficiency. Thymic humoral factor derived from calf thymuses has been demonstrated to have the capacity to restore the immunocompetence of immature, incompetent T cells. This factor was used in the treatment of a 3 1/2-year-old boy who was critically ill with an adenovirus infection and presented evidence of immunocellular deficiency. Within less than 48 hours after the institution of treatment with thymic humoral factor there was a dramatic, progressive clinical improvement, with restoration of the cellular immunocompetence. It is suggested that thymic humoral factor may be beneficial in the treatment of severe viral infections associated with depressed cellular immunocompetence.

Adenoviridae Infections↗

PubMed1997

Integrin alpha5beta1-mediated adenovirus infection is enhanced by the integrin-activating antibody TS2/16.

Adenovirus internalization generally has been accepted to involve an interaction of the adenoviral penton base protein with alpha(v)beta3 and alpha(v)beta5 cell surface integrins. In this study we show that exposure of a panel of melanoma cells to the beta1-activating antibody TS2/16 rendered such cells more susceptible to adenovirus infection. This increase in adenoviral infectivity paralleled effects on cell adhesion, and both these characteristics were mediated, in part, by the alpha5beta1 integrin. These observations suggest that alpha5beta1 may act as an alternative adenovirus receptor and that integrin-activating strategies may improve the efficacy of recombinant adenoviruses as vectors for gene therapy.

Adenoviridae↗

PubMed1993

Nosocomial adenovirus infection in a paediatric respiratory unit.

We report a nosocomial outbreak due to adenovirus in a paediatric respiratory unit serving a poor socio-economic community. Of 207 children admitted during an eight-month period, 24% were neonates; the median age of the remainder was 10 months. Thirty-two cases were found to be infected with adenovirus and of these 67% died. Nine were already infected with adenovirus when admitted. Twenty-three acquired the infection after admission, giving an incidence of nosocomial acquisition of 12% with a 91% mortality rate. All but one of the adenovirus infected children were being ventilated and had an endotracheal tube in place. Nosocomial spread was likely to have been from the hands of attendants, especially those manipulating suction catheters and endotracheal tube or ventilator connections. Risk factors for acquiring nosocomial infection were young age: all but two were < 1 year of age, and a relatively prolonged ward stay necessitated by the nature of the primary condition (pneumonia, bronchiolitis, laryngotracheo bronchitis, tetanus). The measures that were taken to control spread of the virus are described. Despite these, primary cases of adenovirus infection re-introduced the virus regularly over the study period. The genome analysis showed adenovirus types to be 7c2 and 7c.

Adenovirus Infections, Human↗

PubMed1981

Alimentary tract manifestations of bovine adenovirus infections.

Two calves and a feedlot steer with systemic bovine adenovirus infection had hemorrhagic and necrotizing lesions confined to the digestive tract. In one calf there was severe, multifocal, necrotizing, hemorrhagic rumenitis, omasitis, abomasitis, enteritis and colitis. Small intestinal lesions were predominantly in Peyer's patches. Multifocal necrotizing abomasitis was the principal change in the other calf. Large amphophilic intranuclear inclusions typical of bovine adenovirus were common in swollen vascular endothelial cells. Bovine adenovirus was isolated from the former calf. The steer had diffuse hemorrhagic enterocolitis and large numbers of BAV inclusions in vascular endothelial cells of the intestinal lamina propria. Serum-neutralization tests to bovine adenovirus type 3 on acute and convalescent samples from six clinically affected in-contact animals revealed fourfold elevations in two.

Adenoviridae Infections↗

PubMed2001

Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation.

Retrospective analysis of 303 patients who underwent allogeneic hematopoietic stem cell transplantation identified 35 (11.5%) with adenovirus infection. Among them, 22 received specific therapy. As first-line therapy, 18 were treated with intravenous ribavirin, 3 with cidofovir, and 1 with vidarabine. Moreover, 2 received donor leukocyte infusion in combination with ribavirin, and 1 received it after failing to respond to other therapies. Seven survived (31.8%; 3 of 13 who received ribavirin alone and 2 of 3 who received cidofovir). Among the 5 patients treated with combined strategies, 2 who received donor leukocyte infusions showed clearance of all symptoms. Acute graft-versus-host disease grade > or = 3 (P = .01) and a long delay between infection and treatment (P = .05) correlated with a greater risk of treatment failure. In conclusion, ribavirin and vidarabine are ineffective options, particularly for patients at who are high risk of acquiring disseminated adenovirus disease. Conversely, cidofovir or donor leukocyte infusions seem to be encouraging approaches if initiated early.

Adenovirus Infections, Human↗

PubMed1962

Synthesis of virus-specific polymers in adenovirus-infected cells; effect of 5-fluorodeoxyuridine.

Biochemical synthesis in adenovirus-infected HeLa cells was studied utilizing 5-fluorodeoxyuridine (5-FUDR), a potent inhibitor of deoxyribonucleic acid production. Synthesis of saline-soluble DNA and infectious virus was completely suppressed by addition of the analogue to cells as late as 10 hours after infection. The inhibitory effect of this compound was totally reversed by addition of 10(-6)M thymidine to the culture medium. Synthesis of DNA essential for virus production began 10 hours after infection and was completed by 16 hours after infection. These data support the hypothesis that the saline-soluble DNA is a precursor of infectious virus particles. Studies of antigen production indicated that formation of virus-specific proteins was directly dependent upon synthesis of DNA.

Adenoviridae↗

PubMed2002

Biology of ovine adenovirus infection of nonpermissive cells.

Nonhuman adenoviruses, including those of the genus Atadenovirus, have the potential to serve as vectors for vaccine and gene therapy applications in humans, since they are resistant to preexisting immunity induced by human adenoviruses in the majority of the population. In this study, we elucidate the outcome of infection by ovine adenovirus type 7 isolate 287 (OAdV) of several nonovine cell types. We show here that OAdV infects a wide range of nonovine cells but is unable to complete its replication cycle in any of them. In nonovine, nonfibroblast cells, viral replication is blocked at an early stage before the onset of, or early in, DNA replication. Some fibroblasts, on the other hand, allow viral DNA replication but block virus production at a later stage during or after the translation of late viral proteins. Late viral proteins are expressed in cells where viral DNA replication takes place, albeit at a reduced level. Significantly, late proteins are not properly processed, and their cellular distribution differs from that observed in infected ovine cells. Thus, our results clearly show that OAdV infection of all nonovine cells tested is abortive even if significant viral DNA replication occurs. These findings have significant positive implications with respect to the safety of the vector system and its future use in humans.

Adenoviridae↗

PubMed2005

Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation.

Human adenovirus (ADV) infection is an important complication post allogeneic stem cell transplantation (SCT), especially in children, with significant morbidity and mortality despite new antiviral treatment strategies. Although the control of infection seems to require T cells, characterization of ADV-specific T cells post-SCT has not been reported to date. Therefore, we prospectively studied the occurrence of ADV-specific T cells in children with (n = 21) and without (n = 25) ADV-infection postallogeneic SCT and in healthy donors (n = 53). ADV-associated mortality occurred in seven of 21 children. After stimulation ex vivo with ADV-lysate, interferon-gamma-secreting T cells were analysed by flow cytometry. All the patients with ADV-associated mortality had no specific T cells, although reconstitution of absolute lymphocyte counts exceeded 0.3 x 10(9)/l within 30 d post-transplant. Patients who cleared ADV infection had significantly higher frequencies (mean +/- standard deviation, 0.56 +/- 0.5%) of ADV-specific T cells until day 200 post-SCT, than patients without ADV-infection (0.12 +/- 0.1%). These data suggest that ADV-specific T-cell reconstitution is protective against life-threatening ADV-infections postallogeneic SCT.

Adenoviridae↗

PubMedDate not supplied

[Use of the immunofluorescence test in the differential diagnosis of acute and latent adenovirus infections in adult].

Regular laboratory and clinical examinations were carried out in 150 patients with acute respiratory diseases and 25 normal subjects from family foci in whom adenovirus antigen was found in the epithelial cells of the nasal mucosa by means of the immunofluorescence test upon admission. By combinations of various laboratory methods adenovirus infection was confirmed in all the subjects under study. In preparations obtained from normal subjects, predominantly nuclear localization of adenovirus antigen was observed. In patients, localization of the antigen varied. Detection of cells with nuclear localization of adenovirus antigen, the regularity of this localization and the duration of this finding suggest latent infection, whereas findings of cells with cytoplasmic localization of the antigen and an increase in the number of such cells in the course of the disease suggest active adenovirus infection.

Acute Disease↗

PubMedDate not supplied

Adenovirus infection of the duodenum in an AIDS patient: an ultrastructural study.

Intractable diarrhea in a 40-year-old woman with terminal acquired immunodeficiency syndrome resulted from adenovirus infection of the duodenal mucosa. Electron microscopic examination of a duodenal biopsy specimen performed because of clinical suspicion of cryptosporidiosis or microsporidiosis showed pathognomonic viral particles in the nuclei of mucosal epithelium. Extensive sloughing of damaged mucosal cells may have contributed to the diarrhea, for which no other cause was found during either pathologic or microbiologic analysis.

AIDS-Related Opportunistic Infections↗

PubMed2000

The epidemiology of adenovirus infections in Greater Manchester, UK 1982-96.

Data relating to 3313 adenovirus isolates from patients in Greater Manchester, UK between 1982 and 1996 were analysed using chi2 tests and 95% confidence intervals. Of the 3098 isolates that were typed, 18.6% were serotype 2, 14.9% serotype 3, 12.1% serotype 1 and 10.9% serotype 41. There was evidence of a seasonal occurrence of serotype 7 (March-August), serotype 2 (January-April), serotype 4 (June-August) and subgenus F (September-November). Children less than 5 years old were the most common group of patients with adenovirus infection (61.3%) compared to 24.2% for adults and only 5.6% for school children (5-15 years). Gastric symptoms were the most common amongst infants (47.6%) followed by respiratory (27.5%) and general symptoms (12.9%). In adults, the overwhelming clinical condition was conjunctivitis (88.9%). Despite the traditional association with adenoviruses, remarkably few cases of pharyngoconjunctival fever were recorded (1.7%).

Adenoviridae↗

PubMed2001

Screening of rotavirus and adenovirus infections during prolonged hospitalization in a neonatal unit.

UNLABELLED: Rotavirus and adenovirus infections in 308 infants hospitalized for longer than 1 wk, and cases with necrotizing enterocolitis, were screened in a neonatal unit during a 15 mo period, covering two rotavirus epidemics in the community. Altogether, 1020 stool samples were collected weekly until hospital discharge, and in necrotizing enterocolitis cases at the onset of symptoms, and tested for rotavirus and adenovirus by means of enzyme-linked immunosorbent assay. The positive samples were further analysed by polymerase chain reaction. Enzyme-linked immunosorbent assay revealed five adenovirus-positive cases, which were tested negative by polymerase chain reaction. Out of 16 necrotizing enterocolitis cases, one was adenovirus- and another rotavirus positive when tested by polymerase chain reaction, the latter having a concomitant Candida albicans septicaemia. CONCLUSION: Routine rotavirus and adenovirus screening in hospitalized neonates seems to be unnecessary. Viral diagnostic examinations should be considered in patients with necrotizing enterocolitis.

Adenoviridae Infections↗

PubMed1977

Purification of an endonuclease from adenovirus-infected KB cells.

This report describes the purification of an endonuclease from extracts of adenovirus-type-2-infected KB cells. Endonuclease activity can also be detected in extracts of uninfected KB cells and the enzyme activities from extracts of uninfected and adenovirus-infected cells are very similar, if not identical. The enzyme has its maximal activity at pH 4.0. The enzyme found in uninfected and adenovirus-infectedcells is, however, strikingly different from an endonuclease isolated from calf serum. Hence, the endonuclease described is probably not a contaminant derived from the medium in which the KB cells were propagated. The endonuclease in crude extracts from uninfected or adenovirus-infected KB cells can be activated or its activity enhanced by treatment of the extracts with proteolytic enzymes, like pronase or trypsin. Evidence has been presented suggesting that this activation is due to proteolytic cleavage of an inhibitor present in crude extracts of uninfected and adenovirus-type-2-infected KB cells. A second endonuclease has been found in extracts of infected and uninfected cells with optimal activity at pH 7.2 and this endonuclease can be separated from the one with a pH optimum at 4.0.

Adenoviruses, Human↗

PubMed1978

Initiation of transcription in nuclei isolated from adenovirus infected cells.

Initiation of adenovirus transcription was analyzed by incubation of isolated nuclei from virus infected cells in the presence of beta-32P GTP or beta-32P ATP. Nucleotide analysis of RNA from nuclei incubated with beta-32P GTP shows that the label is incorporated exclusively into pppGp and ppGp. Under similar incubation conditions, the label from beta-32P ATP was incorporated primarily into the 5' phosphate of 5', 3' mononucleoside diphosphates, but label was also detected in pppAp, pppGp and in the 3' nucleoside monophosphates. Analysis of RNA, synthesized in the presence of different concentrations of alpha-amanitin, shows that only RNA polymerase III initiates virus specific transcription in isolated nuclei. The virus specific transcripts containing pppAp and pppGp in their 5' termini were identified as the 5.5S and 5.2S viral RNA species by hybridization and finger printing.

Adenoviruses, Human↗

PubMed1998

Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant.

We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable. A renal biopsy showed massive tubular necrosis associated with a prominent granulomatous reaction. The process had a striking regional distribution within the kidney with the injury and inflammation limited to the outer medulla. Adenovirus type 11 was isolated from renal tissue by culture, and adenovirus was demonstrated by immunofluorescence and electron microscopy in the kidney biopsy. Immunosuppression may result in unusual patterns of response to infectious agents. This case demonstrated tropism of the adenovirus to only selected tubules within the kidney, with sparing of other organ function including, specifically, the pancreas allograft. The differential diagnosis of a granulomatous reaction in the transplant kidney must be expanded to include viral infection, in particular, adenovirus.

Adenovirus Infections, Human↗

PubMed1988

Factors responsible for the higher transcriptional activity of extracts of adenovirus-infected cells fractionate with the TATA box transcription factor.

Extracts of adenovirus-infected HeLa cells have 5- to 10-fold-higher activity for transcription from the major late promoter in vitro than do extracts of mock-infected or E1A mutant-infected cells (K. Leong and A. J. Berk, Proc. Natl. Acad. Sci. USA 83:5844-5848, 1986). In this study, we analyzed extracts from mock-infected cells and from cells infected with an E1A mutant, pm975, which expresses principally the large E1A protein responsible for the stimulation of transcription. These extracts were fractionated by phosphocellulose chromatography, a procedure which separates factors required for transcription from this promoter (J. D. Dignam, B. S. Shastry, and R. G. Roeder, Methods Enzymol. 101:582-589, 1983), allowing the quantitative assay of individual factors (M. Samuels, A. Fire, and P. A. Sharp, J. Biol. Chem. 257:14419-14427, 1982). Fractions eluted with 0.04, 0.35, and 0.6 M KCl, which contained RNA polymerase II, the upstream factor MLTF, and three general polymerase II transcription factors, had similar activities when prepared from virus-infected or from mock-infected cells. The sequence-specific DNA-binding activity of MLTF was also similar in the virus-infected- and mock-infected-cell extracts. In contrast, the 1.0 M KCl fraction prepared from virus-infected cells consistently exhibited activity severalfold higher than that of the equivalent fraction prepared in parallel from mock-infected cells. E1A protein eluted principally (greater than 80%) in the 0.35 M KCl fraction. Results of others (M. Sawadogo and R. G. Roeder, Cell 43:165-175, 1985) have shown that the 1.0 M KCl fraction, containing 2 to 5% of the unfractionated protein extract, contains a factor which binds specifically to the major late promoter TATA box. These results, together with a recent genetic analysis of the E1B promoter which demonstrated that the TATA box was required for its efficient transcriptional activation (transactivation) by E1A (L. Wu, D. S. E. Rosser, M. Schmidt, and A. J. Berk, Nature (London) 326:512-515, 1987), are consistent with the model that E1A protein indirectly activates the TATA box transcription factor. Consistent with this model was the finding that mutants of the major late promoter containing only the TATA box and cap site region were transcribed at higher rates with extracts from virus-infected cells than with extracts from mock-infected cells. Other models consistent with the results are also discussed.

Adenovirus Early Proteins↗

PubMed1989

Nontranslated cellular mRNAs are associated with the cytoskeletal framework in influenza virus or adenovirus infected cells.

In an effort to understand the molecular mechanisms underlying the selective shutoff of host protein synthesis in influenza virus and adenovirus infected cells, we analyzed the subcellular location of representative cellular and viral mRNAs. Earlier work has shown that the majority of cellular mRNAs remain polysome associated after infection by either virus and that both the initiation and elongation steps of host protein synthesis were blocked in infected cells (M. G. Katze, D. DeCorato, and R. M. Krug, J. Virol., 60, 1027-1039, 1986). The present study was undertaken to test whether these cellular mRNAs were rendered nontranslatable during infection as a result of their dissociation from the cytoskeleton framework. HeLa cells were fractionated into subcellular components by first gently disrupting the cells with Triton X-100 yielding the soluble fraction (SOL); the cytoskeleton (CSK) fraction was obtained from the Triton insoluble material by the double detergent treatment of Tween-40 and sodium deoxycholate. In uninfected cells the majority of host mRNAs were associated with polysomes which were exclusively bound to the CSK as would be expected of actively translated mRNAs. The cellular mRNAs also remained almost totally associated with the cytoskeleton in adenovirus and influenza virus infected cells despite the fact that these mRNAs are not translated during infection. Indeed, the host mRNAs and the efficiently translated viral mRNAs were CSK associated to the same extent. In contrast to the adenovirus and influenza systems, significant amounts of cellular mRNAs were dissociated from the CSK and found in the SOL fraction of poliovirus infected cells as others have reported. In accordance with the biochemical analysis, morphological studies utilizing electron microscopy revealed that the cytoskeleton remained relatively intact during adenovirus and influenza infection but was substantially reorganized in poliovirus infected cells. We conclude that translational regulatory events are likely different in the poliovirus system and that cytoskeletal association of mRNAs may be required but is not sufficient for efficient mRNA translation during adenovirus or influenza virus infection.

Adenoviridae↗