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PubMed1983

Enteric adenovirus infection in pigs.

Intranuclear adenovirus inclusion bodies were identified in intestinal epithelium by histological, electron microscopical or cytological examination of 43 conventionally raised pigs submitted for diagnostic evaluation from 38 farms between August 1981 and January 1983. The affected pigs were usually less than three weeks old, but ranged from five days to 24 weeks of age. The inclusion bodies occurred in the epithelium of ordinary intestinal villi, or more commonly, in the epithelium covering the blunt villi located over Peyer's patches in the ileum. Fifty-three percent of these adenovirus infected pigs had diarrhea. In most of these pigs with diarrhea (19 of 23) however, agents previously established as causes of porcine enteric disease were also identified. Of the pigs with enterocyte inclusion bodies but without diarrhea, the adenovirus infection appeared incidental to the major disease processes in the pigs. These findings suggest that this adenovirus is an asymptomatic and probably incidental infection in conventional farm-raised pigs.

Adenoviridae Infections↗
PubMed2004

E1B-55-kilodalton protein is not required to block p53-induced transcription during adenovirus infection.

The adenovirus E1B-55-kDa protein binds and inactivates the tumor suppressor protein p53. However, the role of this interaction during infection is still poorly understood and was therefore examined here. Infection with a virus carrying the E1B-55-kDa mutation R239A, preventing the interaction with p53, led to the accumulation of p53. However, p53 target genes were not activated in the infected cells, although p53 phosphorylation did occur and the p53 antagonists Mdm2 and deltaNp73 did not accumulate. Deletion of E4orf6, alone or in combination with E1B-55-kDa, did not allow the induction of p53-responsive genes either. In transient reporter assays, the viral E1A-13S protein antagonized p53 activity; mutational analysis suggested that this depends partially on p300 binding, but it depends even more strongly on the interaction of E1A with the p400/TRRAP protein complex. However, viruses expressing E1A mutants lacking these binding activities, in combination with E1B-55-kDa R239A, still abolished p53 activity. In contrast, when the mutation of E1B-55-kDa at R239A was combined with a deletion of the apoptosis inhibitor E1B-19-kDa, infected cells showed more extensive apoptosis than after infection with single mutants, suggesting that accumulated p53, albeit transcriptionally inactive, might nonetheless enhance apoptosis. Despite extensive apoptosis of the infected cells, the deletion of E1B-19-kDa, in combination with the E1B-55-kDa mutation or in the presence of the constitutively active p53 mutant p53mt24-28, reduced virus replication less than fivefold. In conclusion, adenovirus does not need direct binding of E1B-55-kDa to inactivate p53, and forced p53 activity with consecutive apoptosis does not severely impair virus replication.

Adenovirus E1A Proteins↗
PubMed1980

Adenovirus infection in the immunocompromised patient.

Illness associated adenovirus infection is described in 15 immunocompromised patients. Patients were immunocompromised by severe underlying disease, immunosuppressive or corticosteroid therapy or by age (prematurity). Evidence of adenovirus infection was obtained by either viral isolation or, in two cases, characteristic adenovirus inclusion bodies at postmortem study. All clinical illness was associated with high fever (temperature greater than 39 degrees C). Eighty per cent of the patients had severe systemic complaints including malaise, lethargy, fatigue and night sweats; a similar number of gastrointestinal symptoms. Pulmonary complaints were described in 11 of 15 cases and included cough (67 per cent) and tachypnea (53 per cent). Roentgenologic evidence of pneumonia was demonstrated in 12 of 15 patients (80 per cent). Elevation of serum hepatic enzyme levels (serum glutamic pyruvic transaminase (SGPT)) occurred in eight of 11 patients (73 per cent) and was moderate to severe (serum glutamic pyruvic transaminase greater than 450 IU/liter) in five of 11 (45 per cent). Nine patients died; seven after a rapid downhill course and two after a prolonged illness. Evidence of adenovirus infection microscopically by autopsy in the lung, liver or both is demonstrated in four patients with fulminant systemic illness. Adenovirus infection should be considered in the etiology of severe overwhelming illness in the immunocompromised host.

Adenoviridae Infections↗
PubMed1986

[Changes in the cardiovascular system in adenovirus infection in adults].

The effect of adenovirus infection on the cardiovascular system of 37 adult patients with CHD and without signs of CHD was studied. It was shown that adenovirus infection caused lesion of the cardiovascular system with few clinical signs but with distinct ECG changes. They occurred in the 1st and 2nd weeks and were rather unstable. The most stable and noticeable ECG changes were recorded in CHD patients with a previous history of myocardial infarction and when adenovirus infection was complicated by pneumonia.

Adenoviridae Infections↗
PubMed1995

Enhanced splicing of nonconsensus 3' splice sites late during adenovirus infection.

The adenovirus major late transcription unit is an example of an alternatively spliced gene, in which a common 5' splice site can be spliced to more than 15 different 3' splice sites. Here we show that the specificity in 3' splice site recognition changes during virus infection, such that 3' splice sites with long consensus-type polypyrimidine tracts are repressed while 3' splice sites with short atypical polypyrimidine tracts, which bind U2AF65K inefficiently, are enhanced in splicing in late virus-infected nuclear extracts. On the basis of these experiments, we discuss a mechanism that helps to explain how the complex pattern of major late mRNAs is produced late during virus infection.

Adenoviridae↗
PubMed2003

Clinical assessment of a generic DNA amplification assay for the identification of respiratory adenovirus infections.

BACKGROUND: respiratory adenoviruses are common, often resulting in serious sporadic and epidemic infections and impaired immunity can dramatically increase their severity. They are now thought capable of establishing latency. Diagnosis by culture is slow while direct antigen detection by immunofluorescence lacks sensitivity. Molecular diagnosis can be both rapid and sensitive but the genetic heterogeneity of adenoviruses poses problems. OBJECTIVES: to design a generic adenovirus nested polymerase chain amplification assay designed to be capable of detecting all respiratory adenoviruses. This was achieved through optimised thermal cycling and the development of a generic degenerate primer set targeting the adenovirus hexon gene. STUDY DESIGN: this was a cross-sectional study on 172 respiratory specimens from hospital-based patients, and one from a general practice, in Northern Ireland. A comparison was made between the amplification assay, virus culture and immunofluorescence. RESULTS: the nested polymerase chain reaction (nPCR) assay had a generic capacity for adenovirus detection and an analytical sensitivity of 6.4x10(2) copies/ml. Using an expanded gold standard (defined as a true positive or a true negative where a specimen was positive or negative by at least two of the study assays, respectively), PCR had a clinical sensitivity and specificity of 46/46 (100%) and 15/126 (91.3%), respectively. Patients with acute respiratory adenovirus infections were more likely to be male (chi(2), p=0.005) and to present with a fever (chi(2), p=0.02) than patients diagnosed with another respiratory virus. Co-infection was identified in 12/172 patients. CONCLUSIONS: the nested amplification assay proved highly sensitive in both the analytical and clinical settings for the detection of respiratory adenovirus infections.

Adenovirus Infections, Human↗
PubMed2006

Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation.

During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus-specific donor T cells for adoptive transfer of immunity to patients with HAdV-infection/reactivation. Virus-specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN-gamma) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were infused for adoptive transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV-specific immunity was successful in five of six evaluable patients, documented by a dose-independent and sustained in vivo expansion of HAdV-specific T cells, associated with a durable clearance/decrease of viral copies. T-cell infusion was well tolerated in all nine patients, except one case with graft-versus-host disease II of the skin. In conclusion, induction of a specific T-cell response through adoptive transfer was feasible and effective. When performed early in the course of infection, adoptive T-cell transfer may protect from HAdV-related complications.

Adenovirus Infections, Human↗
PubMedDate not supplied

[Activity of lactate dehydrogenase and its isofractions in experimental asymptomatic adenovirus infections].

Experimentally in 147 dog puppies an asymptomatic infection caused by adenovirus of human origin was produced and the process was caused to become manifest by administration of the same virus against the background of the effect of antilymphocyte serum. The activity of LDG in asymptomatic adenovirus infection was found to decrease in the cytoplasmic fraction of hepatocytes and to increase in the blood serum. An increase in the content of the "hepatic" complex of LDG in the blood serum and its decrease in the cytoplasmic fraction of hepatocytes was established indicating disorders in the liver function. It is concluded that asymptomatic adenovirus infection leads to the formation of the state of pre-pathology. Manifestation of the infection enhances the quantitative aspect of the changes.

Adenoviridae Infections↗
PubMed2005

Adenovirus infection after pediatric bone marrow transplantation: is treatment always necessary?

BACKGROUND: Adenovirus infections are associated with significant rates of morbidity and mortality among children after bone marrow transplantation (BMT). Many transplantation units use molecular virological methods, such as polymerase chain reaction (PCR), for surveillance for adenovirus infection and give preemptive antiviral therapy to children with evidence of disseminated adenovirus infection. This treatment strategy has never been evaluated in clinical trials. METHODS: We retrospectively tested blood samples obtained from a cohort of children who had undergone BMT before the introduction of regular weekly surveillance for adenovirus infection. A total of 273 samples collected from 26 patients between May 1998 and June 2002 were tested for adenovirus infection by quantitative PCR. Virus load was quantified for each sample yielding positive test results, and the clinical notes and virological records of each child were reviewed. RESULTS: Evidence of adenovirus infection was found in 11 children (42%), 7 of whom had not previously had positive test results. Receipt of T cell-depleted transplants was associated with a significantly higher incidence of adenovirus infection during the posttransplantation period. The 2 children who died from adenovirus disease developed infection within 2 weeks after transplantation, and both had very low absolute lymphocyte counts at the time of diagnosis. Seven of 11 children with blood samples that were found to be positive for adenovirus by PCR cleared the virus without antiviral therapy. CONCLUSIONS: Surveillance for adenovirus by PCR is better than symptomatic testing for detecting adenovirus infection. Antiviral therapy may not be necessary for all children who develop adenovirus viremia after BMT.

Adenoviridae↗
PubMed1997

Adenovirus infection inactivates the translational inhibitors 4E-BP1 and 4E-BP2.

Infection with many viruses results in the selective shutoff of host protein synthesis. A common target for virus interference with host protein synthesis is the cap-binding protein complex, eIF4F. The large subunit of the complex, eIF4G, is cleaved upon picornavirus (except cardiovirus) infection. Infection with adenovirus and influenza virus causes dephosphorylation of the cap-binding subunit, eIF4E. Recently, it has been shown that infection with poliovirus or encephalomyocarditis virus activates 4E-BP1, which is a specific inhibitor of eIF4E. Here we show that early in adenovirus infection, 4E-BP1 and its related protein 4E-BP2 are phosphorylated and hence inactivated. This is not consistent with a role of 4E-BPs in adenovirus-induced shutoff, but could explain the increase in protein synthesis reported early in infection. Phosphorylation of 4E-BP1 and 4E-BP2 is consistent with earlier findings in adenovirus-infected cells on the activation of the protein kinase p70(S6k), whose phosphorylation lies on the same pathway as 4E-BPs, by E1A. Findings similar to those described here were reported for 4E-BP1 by D. Feigenblum and R. J. Schneider (1996, Mol. Cell. Biol. 16, 5450-5457).

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

[Cytochemical study of granulocyte enzymes in germ-free animals with adenovirus infections].

The activity of some dehydrogenases and hydrolases was studied by cytochemical methods in the peripheral blood neutrophils of germ-free guinea pigs infected with adenoviruses. The gnotobiotic animals were obtained by hysterotomy in an operation isolation room after which they were transferred into manipulation isolation room and infected with human adenovirus type 1. A depression of enzymes of alpha-glycerophosphate shunt and NADP-H2-diaphorase in neutrophils two days after infection and activation of lactate dehydrogenase and acid phosphatase at 4 days were demonstrated. The pattern of changes in the enzymatic status of intact and infected gnotobiotic animals allowed a diagnosis of adenovirus infection in most cases.

Acid Phosphatase↗
PubMedDate not supplied

Disseminated adenovirus infection with hepatic necrosis in patients with human immunodeficiency virus infection and other immunodeficiency states.

Disseminated adenovirus infection with fatal hepatic necrosis has been reported in 16 patients, 15 of whom had immunocompromising conditions. Herein we report three patients with AIDS and fatally disseminated adenovirus infection with hepatic necrosis. The median age of these 16 patients was 4.7 years, and their illness was characterized by fever (13 of 16 patients), coagulopathy (10 of 16), lower respiratory tract disease (10 of 16), and gastrointestinal hemorrhage (five of 16) in addition to clinical evidence of hepatitis. The adenoviruses isolated were the commonly found serotypes 1, 2, 3, 5, and 7 for 13 of the 15 cases for which this determination was available. With the high frequency of adenovirus infection in humans and the increasing prevalence of human immunodeficiency virus infection in children, it seems likely that this syndrome will continue to be seen.

Adenoviridae Infections↗
PubMed2001

Prediction of severe disseminated adenovirus infection by serum PCR.

Adenoviruses are increasingly recognised as viral pathogens that can cause fatal infections in immunocompromised patients, particularly recipients of haematopoietic stem-cell grafts. Adenovirus infections are not easily diagnosed and the development of a severe infection cannot be predicted by standard culture techniques. In a pilot study, we investigated the value of adenovirus DNA detection in serum as a marker of disseminated disease in 14 patients with defined patterns of adenovirus infections. The results show that the appearance of adenoviral DNA in serum preceded the development of a severe or fatal adenovirus infection. Because proper management is dependent on early diagnosis and differentiation from other conditions, this test may be a valuable tool in the management of adenovirus infection.

Adenovirus Infections, Human↗