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At least 253 records · Page 14Linked to original sources

Failure of intravenous ribavirin in the treatment of invasive adenovirus infection following allogeneic bone marrow transplantation: a case report.

We report a case of fatal adenovirus infection in a 37-year-old female who underwent allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML). Post BMT she developed acute grade II graft-vs.-host disease (aGVHD) requiring high-dose steroids and anti-thymocyte globulin. Additionally, her clinical course was complicated with adenovirus-associated haemorrhagic cystitis and viraemia. Intravenous ribavirin was obtained and administered for 5 days without success; the patient's mental status deteriorated rapidly and she died on day 69 post-transplant. Radiological imaging revealed diffuse cortical necrosis. At autopsy adenovirus was identified in her bladder, kidneys and lungs.

Adenovirus Infections, Human↗

Nature and specificity of effector cells in cell-mediated cytolysis of mouse adenovirus-infected cells.

The type of effector cells in immune spleen cells (ISC) responsible for cell-mediated cytolysis of mouse adenovirus-infected cells was characterized. When ISC were pretreated with anti-mouse thymocyte or anti-Thy1.2 serum and complement, their cytolytic activity assayed by the (51)Cr release test was completely abolished, whereas it was not significantly reduced either when ISC were pretreated with anti-mouse immunoglobulin serum and complement or after ISC were kept standing at 37 degrees C for 2 h in a plastic dish to remove adherent cells. These data indicate that the effector cells in ISC are T cells. The release of nonspecific or specific soluble cytotoxic factor(s) from ISC upon contact with mouse adenovirus-infected cells was not demonstrated, but about 30 U of interferon activity per ml was detected. However, 10 times as many units of exogenous interferon or more showed no effect on (51)Cr release from target infected cells or on the inhibition of viral antigen synthesis in infected cells. Experiments with mouse cells of different major histocompatibility antigens indicated that the cytotoxicity of ISC is effective when sensitizer and target cells share all or part of the same H-2 gene complex but not effective when they are of a different H-2 gene complex.

Adenoviridae↗

A population-based prospective survey of newborn infants with suspected systemic infection: occurrence of sporadic enterovirus and adenovirus infections.

BACKGROUND: Enterovirus outbreaks are known to occur in neonatal wards and enteroviruses may cause community-acquired sepsis-like disease in the neonatal period. Less well is known their possible role in suspected systemic infections during the perinatal period. OBJECTIVES: To investigate the occurrence of enterovirus infections in neonatal patients suspected of systemic infection. STUDY DESIGN: A population-based prospective survey was organized in the hospitals of the Greater Helsinki Region during 13 months in 1993-94. Criteria for enrollment included onset of symptoms before the age of 29 days and a decision, on clinical grounds, to take a blood culture for bacteria. Acute phase samples of blood, feces, nasopharyngeal swab, and cerebrospinal fluid, if available, were inoculated in monolayer cultures of four different cell lines. In addition, enterovirus infections were searched for using an enterovirus group-reacting IgM test. RESULTS: One hundred and thirty-seven patients had a sufficient number of specimens examined, and were thus evaluable. Most of the infants had the onset of the symptoms within a few days after birth. An enterovirus was isolated from four newborn infants (3%), while seven children (5%) were found to excrete adenovirus. Enteroviral antigen was detected in cell cultures inoculated with specimens from two additional infants. Virus-positive infants had no evidence of bacterial infection and did not show specific clinical signs or symptoms differentiating them from the rest of the study group. All enrolled infants recovered without sequelae. CONCLUSION: We conclude that sporadic viral infections may be common in neonatal patients with suspected systemic infection, and this should be taken into account when judging the etiology.

Adenoviridae Infections↗

Synthesis of complementary RNA sequences during productive adenovirus infection.

Liquid RNA.DNA hybridization with separated strands of adenovirus type 2 DNA revealed that late nuclear RNA can hybridize to about 85% of the 1-strand and 10-15% of the h-strand, whereas late cytoplasmic RNA hybridizes to 65-70% and 25% of the l- and h-strand, respectively. With separated strands from the six EcoRI fragments of adenovirus type 2 DNA as probes, it was shown that late nuclear RNA hydridizes to 85-90% of the l-strand from all six EcoRI fragments. Since late cytoplasmic RNA hybridizes to 40-50% of the h-strand from both fragments EcoRI-B and EcoRI-C, complementary viral RNA sequences are synthesized during adenovirus infection. Complementarity between nuclear and cytoplasmic RNA could also be demonstrated by showing that late cytoplasmic RNA which had been preincubated with late nuclear RNA hybridized to a smaller fraction of the h-strand of fragment EcoRI-C than without preincubation. Double-stranded RNA which contains sequences that correspond to at least 60% of the viral genome was isolated from infected cells. However, less than 2% of the newly synthesized late RNA became double-stranded after incubation under annealing conditions, which suggests that RNA derived from one of the strands is present at a low concentration. Accordingly, it was shown that nearly all viral cytoplasmic RNA which is synthesized late after infection is derived from the l-strand.

Adenoviridae↗

One-year prospective cross-sectional study to assess the importance of group F adenovirus infections in children under 2 years admitted to hospital.

A 1-year prospective cross-sectional study of 363 children under 2 years of age admitted to hospital was undertaken to assess the importance of group F adenovirus infections. Faeces obtained within 48 hours of admission from 97 patients with and 266 patients without diarrhoea were screened by electron microscopy. Viruses were identified by morphological criteria, and all adenoviruses seen were retested by immune electron microscopy to identify group F serotypes. Group F adenoviruses (4 infections) were second in frequency to rotaviruses (16 infections), and both viruses were significantly associated with diarrhoea (P = 0.005 and 0.00001 respectively, chi-squared test). All four group F infections occurred in children with diarrhoeal disease aged between 1 and 6 months and were numerically as important as rotavirus (three infections) in this group. Rotavirus infections occurred significantly more frequently in the 7-24-month age group with diarrhoea (11 v.0 infections, P = 0.001, chi-squared test). Nosocomial infection occurred with group F adenovirus as well as rotavirus. The finding that group F adenoviruses occur as frequently as rotaviruses in diarrhoeal disease that results in hospital admission in children between 1 and 6 months of age could have important implications for preventative strategies.

Adenoviridae Infections↗

Hepatitis B virus X protein partially substitutes for E1A transcriptional function during adenovirus infection.

Lack of an in vitro culture system for human hepatitis B virus has hampered the ability to address fundamental questions regarding the viral life cycle and the effect of viral gene products during productive infection. To study the activity of HBV X protein (HBx) in the context of a viral infectious cycle, we provided HBx in trans during adenovirus infection of liver-derived cells. In hepatoma cells infected with adenovirus mutants deficient in expression of various E1A products, HBx was able to partially substitute for the transcriptional activation function of E1A. HBx also activated adenovirus replication, but to a lesser extent than the activation of transcription. Adenovirus genes transcribed by either RNA polymerase II or RNA polymerase III were activated by HBx during infection. These results suggest that HBx and E1A activate transcription by a similar mechanism and that this viral infection system will be useful for characterization of the functional activities of HBx.

Adenovirus E1 Proteins↗

Activation of focal adhesion kinase in adenovirus-infected human corneal fibroblasts.

PURPOSE: Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase with protean downstream influences on cell cycle regulation, cytoskeletal dynamics, and cell attachment, is activated by integrin binding and aggregation. Adenoviruses, including those associated with human keratitis, enter permissive cells by an integrin-mediated mechanism. Hence, a possible relationship between adenovirus infection and tyrosine phosphorylation of FAK in human corneal cells was explored. METHODS: Human corneal fibroblasts (HCFs) derived from donor corneas were infected for various periods with adenovirus type 19 (Ad19) or were mock infected with virus-free medium. Parallel experiments included echistatin, which is a snake venom disintegrin and a partial inhibitor of FAK. For immunoblot analysis, Triton-X-soluble and Triton-X-insoluble fractions were analyzed by SDS-PAGE and immunoblotted with phosphospecific antibodies. Expression of the interleukin (IL)-8 gene was analyzed by RT-PCR and ELISA. RESULTS: Ad19 infection of HCFs induced tyrosine phosphorylation of a protein at 125 kDa, which was evident within 15 minutes after infection and was established by immunoprecipitation to be FAK. Immunoblot with antibody to FAK tyrosine-397 confirmed phosphorylation of this key binding site for downstream signaling proteins. Immunoblot analysis further suggested a shift in the intracellular location of phosphorylated FAK from the cytosol (Triton-X-soluble cell lysate fraction) to the cytoskeleton (Triton-X-insoluble cell lysate pellet) on infection. Finally, treatment of HCFs with echistatin reduced virus-induced expression of the neutrophil chemotaxin IL-8, previously implicated in adenoviral pathogenesis. CONCLUSIONS: Ad19 infection of HCFs induces rapid phosphorylation of FAK, and a dramatic change in its intracellular distribution. Activation of FAK may contribute to the inflammatory response to adenovirus infection of the human cornea.

Adenoviruses, Human↗

Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not induce cell surface presentation of the La (SS-B) autoantigen.

Antibodies to the RNA polymerase III transcription termination factor La are frequently found in the serum of patients with various autoimmune diseases. The mechanisms by which autoimmune responses are evoked remain largely obscure, but the presentation of autoantigens on the cell surface during stress conditions has been reported as a possible factor. In this study we analysed the effects of adenovirus infection on the binding of anti-La antibodies to the surface of several human cell lines and on the levels of the membrane-expressed glycoproteins HLA class I, CD44 and the CD3 complex. In addition, we studied the relative amount and the intracellular distribution of the La protein as well as its association with the major species of non-coding virus-associated (VAI) RNA. While immunofluorescence patterns revealed a redistribution and possibly cell surface expression of the La protein during infection, this could not be confirmed by other techniques. In contrast, surface levels of HLA class I proteins and CD3 complex were severely affected. The data suggest that the subcellular distribution of the La protein is not detectably influenced by adenovirus infection.

Adenovirus Infections, Human↗

[Bronchopneumonia, obstructive bronchitis and bronchiectasis in children with adenovirus infections].

During the five-year period 56 children were treated in hospital due to respiratory infections caused by adenovirus. Clinical, laboratory and radiographic signs of the illness are presented. The infections manifested as the upper respiratory tract infection in 3 patients (5.4%), obstructive bronchitis in 16 patients (28.6%), bronchopneumonia in 32 patients (57.1%) and bronchiectasis in 5 patients (8.9%). Three children were operated: bilobectomy was performed in two cases, and left-sided pulmonectomy in one case. Histologically, bronchiectasis was found in two cases and bronchiolitis obliterans in one case. In this work we tried to show the gravity, importance and consequences of the adenoviral infection of the respiratory tract in children.

Adenovirus Infections, Human↗

Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection.

A cDNA copy of the major human heat shock mRNA was cloned. The clone is complementary to the mRNA encoding the major 70-kilodalton heat shock protein as shown by hybrid arrest translation. We utilized the cloned DNA to measure induction of the gene during adenovirus infection. The mRNA increases in abundance approximately 100-fold during a wild-type adenovirus infection but does not increase more than 2-fold during an infection in which there is no E1A gene function [high multiplicity of infection of an E1A (-) mutant]. Furthermore, by measuring transcription in isolated nuclei, we found that the induction was transcriptional and was mediated by the E1A gene product. The induction was not maintained, however. After a peak level was obtained, transcription returned to preinfection levels. This decline was also reflected in the cytoplasmic mRNA abundance indicating a rapid turnover of the heat shock mRNA. This rapid turnover of the heat shock mRNA appears to be induced by the viral infection since the heat shock mRNA was found to be stable when synthesized in an adenovirus-transformed cell line.

Adenoviridae↗

Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients.

Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had severe manifestations of infection. Cidofovir treatment led to clinical improvement in 8 of 10 patients with severe infection and to virologic clearance in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12 clinical adenovirus isolates. Cidofovir is a promising treatment option for this population.

Adenoviridae↗

ICAM-1 expression on bronchial epithelium after recombinant adenovirus infection.

Early experience with recombinant adenoviruses for gene transfer to airway epithelium suggests that these vectors are associated with the development of inflammation. The mechanisms for this are unclear, but previous work has shown that respiratory viruses can cause increased expression of intercellular adhesion molecule-1 (ICAM-1) on airway epithelial cells. We therefore hypothesized that recombinant adenoviruses may induce ICAM-1 expression and thereby facilitate the development of airway inflammation. To address this, primary cultures of human bronchial epithelial cells were examined for ICAM-1 expression by flow cytometry after infection with a serotype 5, E1/E3-deleted recombinant adenovirus containing the Escherichia coli LacZ reporter gene driven by the cytomegalovirus promoter (Ad.CMVlacZ). Compared with control cells, ICAM-1 expression was unchanged after infection with Ad.CMVlacZ, but increased after infection with wild-type adenovirus. Treatment of Ad.CMVlacZ-infected cells with interferon-gamma (IFN) resulted in increased ICAM-1 expression, but to a lower level than that seen in cells treated with IFN alone, indicating that recombinant adenovirus infection blunted IFN-induced up-regulation of ICAM-1. Adhesion of human leukocytes to human bronchial epithelial cells was not increased after Ad.CMVlacZ infection, thereby excluding an ICAM-1-independent increase in leukocyte-epithelial adhesion. The results for ICAM-1 expression were confirmed in vivo, as immunostaining of human bronchial xenografts infected with Ad.CMVlacZ revealed basilar epithelial staining with ICAM-1, but no increased expression on cells expressing beta-galactosidase. This study demonstrates that unlike other respiratory viruses, recombinant E1/E3-deleted adenovirus does not cause increased ICAM-1 expression on human bronchial epithelium in vitro or in vivo nor increased leukocyte adhesion in vitro.

Adenoviridae↗

An immune dot-blot technique for the diagnosis of ocular adenovirus infection.

The development of a monoclonal antibody based radio-immune dot-blot technique (IDBT) for the rapid detection of adenovirus is described. 718 conjunctival swabs from patients with acute keratoconjunctivitis were examined by conventional cell culture isolation techniques and IDBT. IDBT identified adenovirus in 64 of 75 culture positive samples and also in a further 34 culture negative samples [Sensitivity (IDBT versus culture) 85.3%; Specificity 92.2%]. IDBT is considered to be a simple, clinically relevant, technique for the rapid identification of adenovirus infection of the eye.

Adenovirus Infections, Human↗

Fatal adenovirus infection indistinguishable from thrombotic microangiopathy after allogeneic CD34+ peripheral progenitor cell transplantation.

A 10-year-old boy with acute lymphoblastic leukemia in second relapse received CD34+ purified allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical father. The patient developed grade II acute GVHD and received high-dose methyl-prednisolone starting on day + 13 posttransplant. Renal dysfunction followed by massive gastrointestinal bleeding was observed from day + 14. The laboratory findings including elevated serum LDH, increased RBC fragmentation, higher level of thrombomodulin and undetectable haptoglobin corresponded with the diagnosis of thrombotic microangiopathy (TMA). In spite of various treatments, the patient died of multiple organ failure on day + 93. Post-mortem examination revealed systemic adenovirus infection without histological findings of TMA. Severe adenovirus infection may be confused with TMA, and should be distinguished by rapid virological assay.

Adenoviridae Infections↗

Control of translation in adenovirus-infected cells.

The initiation of protein synthesis in adenovirus-infected cells is regulated during the late phase in two ways, which may be related. The overall translation rate is maintained by a small viral RNA, VA RNAI, which prevents the phosphorylation of initiation factor eIF-2 by a double-stranded RNA-activated protein kinase, DAI. In addition, the relative efficiency of translation of host cell and viral mRNA populations is regulated in the infected cell during the late phase such that viral mRNAs are selectively utilized. Three viral elements have been implicated in this process: the 5' leader present on most late viral mRNAs; the late protein, 100K; and VA RNA. This article reviews the mechanisms underlying these translational control phenomena.

Adenoviridae↗

Adenovirus infections in hematopoietic stem cell transplant recipients.

We report a 12% incidence of adenovirus infections among 532 recipients of hematopoietic stem cell transplant (HSCT) from January 1986 through March 1997. The median time from day of stem cell infusion to first positive culture was 41 days. Recipients of allogeneic stem cells, as opposed to autologous stem cell recipients, were more likely to have a culture positive for adenovirus (16% vs. 3%; P<.0001). Pediatric patients were also more likely than adults to have a positive culture (23% vs. 9%; P<.0001). Among stem cell recipients with partially matched related donors, pediatric recipients appear to be at significantly greater risk for infection than adult recipients (P<.001). Positive cultures were associated with evidence of invasion in 64% of cases (41 of 64). A multiple logistic regression analysis showed that isolating adenovirus from more than 1 site correlated with greater risk for invasive infections (P=.002). Invasive infections were associated with poorer chance of survival.

Adenovirus Infections, Human↗