PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “ADENOVIRUS INFECTIONS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2002

In vivo association of adenovirus large E1A protein with the human mediator complex in adenovirus-infected and -transformed cells.

The adenovirus large E1A protein activates transcription from early viral promoters by a mechanism that requires a forty amino acid zinc finger activation domain in E1A conserved region 3 (CR3). Recent results indicate that activation by a Gal4 DNA-binding domain-E1A-CR3 fusion requires an interaction between the E1A-CR3 zinc finger and the Sur2 subunit of the mammalian Mediator (of transcription) complex. Although several host proteins have been shown to bind stably to E1A proteins in adenovirus-infected and -transformed cells, an in vivo interaction with Mediator complex subunits has not been described previously. Using immunoprecipitation and gel filtration analyses of nuclear extracts prepared from HeLa cells infected with adenovirus 5 or mutants that express either large or small E1A specifically and from adenovirus 5-transformed cells, we report here that large E1A, but not small E1A, binds to Mediator complex in vivo. Only approximately 1 to 10% of large E1A is bound to Mediator complex at 18 h postinfection and in transformed cells, probably explaining why Mediator complex subunits were not identified among cellular E1A-binding proteins described earlier. Surprisingly, even though extracted Mediator can quantitatively bind to an E1A-CR3 affinity column, only on the order of 1% of cellular Mediator complex is bound by E1A in vivo. Much of the large E1A bound to Mediator in 293 cells is in a stable complex that includes RNA polymerase II, leading us to suggest that the interaction of E1A-CR3 with Mediator stabilizes the interaction of Mediator with the polymerase. This stabilization of the interaction between Mediator and RNA polymerase II may contribute to the mechanism of activation by E1A-CR3.

Adenovirus E1A Proteins↗
PubMed2005

Adenovirus infection rates in pediatric recipients of alternate donor allogeneic bone marrow transplants receiving either antithymocyte globulin (ATG) or alemtuzumab (Campath).

Infectious complications due to adenovirus are of increasing concern after allogeneic stem cell transplantation. Over the past 4 years, we have modified our conditioning regimens to use alemtuzumab in preference to anti-thymocyte globulin (ATG) for pediatric patients receiving stem cell transplants from alternate donors. Recent reports in adult studies implicate alemtuzumab as a risk factor for adenovirus infection. We therefore evaluated the incidence of adenovirus infection in pediatric patients receiving either ATG or alemtuzumab in their conditioning regimens. Of the 111 patients evaluated, a total of 54 patients received ATG and 57 patients received alemtuzumab. In total, 35/111 (32%) patients were infected by adenovirus, and 9/111 (8%) had adenovirus disease (AD). Adenovirus infection was greater in the alemtuzumab group than the ATG group (23/57 vs 12/54) (P=0.039) and disseminated AD was more frequent in the alemtuzumab group vs the ATG group (8/57 and 1/54 respectively) (P=0.032). The presence of Grade 3-4 graft-versus-host disease was a risk factor for adenovirus infection. Our findings highlight the fact that adenovirus infection is a frequent complication after stem cell transplantation from alternate donors in the pediatric population and that alemtuzumab increases the risk of infection compared to ATG. This work will help in identifying at-risk populations for our upcoming immunotherapy trial using adoptively transferred donor-derived adenovirus-specific cytotoxic T lymphocytes.

Adenovirus Infections, Human↗
PubMed1995

The metabolism of small cellular RNA species during productive subgroup C adenovirus infection.

During the late phase of subgroup C adenovirus infection, export of cellular mRNA from the nucleus to the cytoplasm is inhibited. In one approach to investigate the mechanism whereby viral late mRNAs are selected for export, we have examined the metabolism of small cellular RNA species transcribed by all three RNA polymerases during the late phase of Ad5 infection. No changes in the quantities of [3H]uridine-labeled 5S rRNA or tRNAs entering the cytoplasm were observed in infected cells. Adenovirus type 5 infection reduced the nuclear and cytoplasmic populations of the newly synthesized, snRNP-associated snRNAs U1, U2, U4, U5, and U6. Transcription of a representative snRNA, U1 RNA, was not inhibited, indicating that the post-transcriptional metabolism of snRNAs was perturbed during the late phase of infection. The increased cytoplasmic concentration of newly synthesized U1 RNA in Ad5- compared to mock-infected cells, and the greater reduction of the snRNP-associated compared to the total U1 RNA population, indicated that snRNP assembly in the cytoplasm was impaired. As adenovirus infection does not perturb export from the nucleus of small cellular mRNAs transcribed by RNA polymerases II and III, viral mRNA must be distinguished for selective export at a nuclear step upstream of translocation to the cytoplasm via nuclear pore complexes.

Adenoviridae↗
PubMedDate not supplied

Diagnosis of avian adenovirus infections using DNA in situ hybridization.

Three DNA oligonucleotide probes designated FN-23, FN-48, and FN-96 were evaluated for the diagnosis of aviadenovirus infections by DNA in situ hybridization. Paraffin-embedded tissues were obtained from birds with confirmed adenovirus infection, birds with putative adenovirus infections, and birds with intranuclear inclusions caused by herpesvirus and polyomavirus. In birds with confirmed adenovirus infection, probes FN-23 and FN-96 identified 78% and 72% of diseased individuals, respectively. Only probe FN-48 detected chickens with group II adenovirus infection. In birds with putative adenovirus infection, the DNA probes confirmed aviadenovirus infections in 76% of the population. Probes FN-23, FN-96, and FN-48 detected 85%, 74%, and 18% of adenovirus-infected birds, respectively. None of the DNA probes cross-hybridized with tissues from polyomavirus-infected psittaciform birds or with tissues from a chicken with infectious laryngotracheitis. In contrast, probe FN-23 did cross-hybridize to herpesvirus-infected tissues from two of eight psittaciform birds with Pacheco's parrot disease. Probes FN-48 and FN-96 did not react with these tissues.

Adenoviridae Infections↗
PubMed1992

Retention of epidermal growth factor receptors in the endoplasmic reticulum of adenovirus-infected cells.

The epidermal growth factor (EGF) receptor is down-regulated during early infection with adenovirus, and this has been attributed to accelerated internalization and degradation of the receptor in the absence of ligand (Carlin, Tollefson, Brady, Hoffman & Wold (1989) Cell 57, 135-144]. Using pulse-chase analysis, we show that loss of functional EGF receptors after infection of human KB and A431 cells with adenovirus type 5 is accompanied by accumulation of a receptor precursor that remains fully sensitive to endoglycosidase H, indicative of retention in the endoplasmic reticulum. A truncated receptor, normally secreted by A431 cells, also accumulates intracellularly as an endoglycosidase H-sensitive precursor. In no case is the block in intracellular transport of EGF receptors complete. We conclude that both stimulation of EGF receptor internalization and degradation and inhibition of intracellular transport of newly synthesized EGF receptors from the endoplasmic reticulum towards the cell surface contribute to EGF receptor down-regulation in adenovirus-infected cells.

Adenoviruses, Human↗
PubMed2000

Expression of a human coxsackie/adenovirus receptor transgene permits adenovirus infection of primary lymphocytes.

Replication-defective adenoviruses are effective vehicles for gene transfer, both for the repair of defective genes and for studies of gene function in primary cells. Many cell types, including lymphocytes, are refractory to adenovirus infection because they lack the Coxsackie/adenovirus receptor (CAR) needed for virus attachment. To extend the advantages of adenovirus-mediated gene transfer to primary lymphoid populations and other cell types lacking endogenous CAR, we produced a mouse that expresses human (h) CAR as a transgene under control of a murine MHC class I promoter. hCAR protein is expressed on T and B lymphocytes from a variety of organs (spleen, lymph node, bone marrow, thymus, and peritoneum). These lymphocytes are susceptible to adenovirus infection, as demonstrated by reporter green fluorescent protein gene expression, with the fraction of expressing cells as high as 70%. Some lymphocyte subpopulations required stimulation subsequent to adenovirus infection for reporter expression. This activation requirement is a restriction imposed by the promoter used in the adenovirus construct. In subpopulations requiring activation, the elongation factor 1 promoter was far superior to a hCMV promoter for directing green fluorescent protein production. We also find that hCAR mRNA is produced in nonlymphoid tissues from all founder lines, including tissues that do not express endogenous murine CAR, suggesting the opportunity for effecting gene delivery to and testing gene function in a wide variety of primary cell types previously resistant to gene transfer.

Adenoviridae↗
PubMed1991

Stabilization of actin filaments at early times after adenovirus infection and in heat-shocked cells.

Human cells (HEp-2) infected with adenovirus type 5 (Ad5) at early times (5-7 h) after infection exhibit stabilization of the filamentous actin network against disruption by latrunculin (300-2000 ng), a potent microfilament toxin. This protection is abrogated by pretreatment of infected cells with cycloheximide, suggesting that it is due to a protein induced early after Ad5 infection. Support for a role of HSP70 (heat shock protein of Mr = 70 kDa) in actin stabilization is based on several findings; (i) HSP70 is induced at early times post-infection in Ad5-infected HEp-2 cells, (ii) heat shock treatment (42 degrees C) of uninfected HEp-2 or HeLa cells results in a rearrangement of actin filaments around the nucleus, that is resistant to disruption by latrunculin, (iii) using a DNase I inhibition assay, the percentage of filamentous actin increases from 50 to 65% of total following heat shock of uninfected cells, and (iv) HSP70 induces actin polymerization from monomers in vitro.

Actins↗
PubMed2002

Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery.

Adenovirus infections occur in 5% to 21% of patients following stem cell transplantation (SCT), with an associated mortality of up to 50%. However, a lack of prospective studies has hampered further developments in the understanding and management of this infection in the posttransplantation setting. We prospectively studied the incidence and outcome of adenovirus infections after SCT using preemptive screening and a policy of reduction or withdrawal of immunosuppressive therapy if the virus was isolated. The incidence of adenovirus infection was 19.7% (15 of 76), and the virus was isolated exclusively in recipients of T-cell-depleted grafts. Patients receiving 50 or 100 mg alemtuzumab in vivo were at the greatest risk of adenovirus infection (45% probability) regardless of donor type, and this was related to the slower lymphocyte recovery. Six (40%) of the 15 adenovirus-infected patients developed adenovirus disease. Severe lymphocytopenia (less than 300/microL) at the time of first detection of adenovirus was a major risk factor for development of adenovirus disease (P =.001). In addition, failure to reduce immunosuppression (P =.04) and a positive result of adenovirus polymerase chain reaction (PCR) in blood at diagnosis (P =.01) were both associated with fatal adenovirus disease. On the basis of this study, we recommend active surveillance for adenovirus infection in T-cell-depleted SCT and withdrawal or reduction of immunosuppressive treatment, if possible, in patients with adenovirus infection. Preemptive antiviral therapy is warranted for patients with severe lymphocytopenia or positive blood PCR, and in those in whom immunosuppressive therapy cannot be reduced.

Adenoviridae Infections↗
PubMed1990

[The role of secretory antibodies in adenovirus infection].

The protective role of secretory antibodies in the development of adenovirus infection has been established. More severe and prolonged course of adenovirus infection, accompanied by the involvement of the lower respiratory tract in the process, has been noted in patients with low titers of antibodies, or their absence, in secretions (O to 1:4). The presence of secretory antibodies in a titer of 1:8 considerably alleviated the course of the disease. The antibody titer 1:16 (according to the data of the passive hemagglutination test) has proved to be protective for children and adults in adenovirus infection. The results of the determination of antibodies in the secretions of the upper respiratory tract in the passive hemagglutination test may be used for the purposes of prognostication.

Acute Disease↗
PubMed1992

Effect of adenovirus infection on adiposity in chicken.

Excessive fat accumulation has been observed in the field in chickens infected with adenovirus. In the present study this has been verified under experimental conditions. Chickens inoculated with adenovirus showed lesser weight gain but excessive adiposity compared to normal control chickens. These changes could not be explained by variation in food consumption. Chickens acquiring adenovirus naturally from the inoculated group showed similar adiposity. Serum cholesterol and triglyceride levels of inoculated and naturally infected chickens were significantly lower compared to those of the control group. Such an association between adenovirus infection and adiposity has been shown, probably, for the first time, which might help in further understanding of the complex problem of obesity.

Adenoviridae Infections↗
PubMed1989

Clinical and laboratory findings in children with adenovirus infections.

The hospital records of 49 children with adenovirus infection were reviewed. Diagnosis was made by virus isolation from the airways in 73%, the stools in 44%, the conjunctiva in 2% and by serology in 14% of the patients. Most children were less than 3 years of age. The peak incidence of virus isolation occurred during the month of April. Pharyngotonsillitis was the most frequent main diagnosis (49%), followed by pneumonia (14%), gastroenteritis (10%) and bronchitis (8%). Fever was the most frequent main symptom (43%), and 96% of the patients had fever at some time during the illness. The average fever temperature was 39.6 degrees C with a mean duration of 5.9 days. An obvious bacterial superinfection could be demonstrated in three patients: two had otitis media and one had pneumonia with pleural effusion. All three had more than 3 band forms per 100 peripheral white blood cells, whereas only 1 out of 46 children without demonstrable superinfection had an elevated band count. Other laboratory tests were not useful in detecting bacterial superinfection. That 71% of all children received antibiotics at some time during their illness, reflects the difficulty of excluding bacterial disease.

Adenoviridae Infections↗
PubMed1983

Effect of adenovirus infection on human peripheral lymphocytes.

The effect of adenovirus infection on human peripheral lymphocytes has been studied in vitro. Virus antigens were found to multiply in the cell cultures but no infective virus was formed. On infecting the lymphocytes after stimulation with phytohaemagglutinin, infective virus was formed though in low titre. Adenovirus infection decreased the E-rosette forming activity and the response to phytohaemagglutinin of the lymphocytes. The immunomodulating drug levamisole failed to influence significantly the effect of the virus. Adenovirus thus causes several changes in the characteristics of peripheral lymphocytes which may lead to a disturbance of the immune function.

Adenoviridae Infections↗
PubMedDate not supplied

[Fatal cases of adenovirus infection].

Sixteen fatal cases of adenovirus infection in infants (n:10 aged 1 to less than 12 months) and children (n:6 aged 1 to 3, 8/12 years) are reported. Diagnosis were confirmed by direct viral isolation, viral immunofluorescence or both in 15 patients, and by autopsy in 12 of them, including one without positive virological workup. Evidence of multisystemic compromise, particularly that of severe lower respiratory tract infection was observed and lead to death by acute respiratory failure in all cases. White blood cell counts and erythrocyte sedimentation rate did not help to label initially the etiology as either viral or bacterial. Chest roentgenograms showed pulmonary over-inflation and evidence of pneumonitis as well as extensive and rapidly progressive lung opacifications. Most prominent pathologic findings were necrotizing bronchitis, bronchiolitis and broncopneumonia. Several cells containing typical intranuclear inclusion bodies were documented in ten cases and pneumonitis was the only finding in two. Hepatic fat infiltration and lymphocitic depletion of thymus, spleen and lymphatic nodes occurred in all cases. The need of rapid diagnostic tools to avoid nosocomial spread of this kind of infections with such serious consequences is stressed.

Adenovirus Infections, Human↗
PubMed1997

Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression.

Previous studies have shown that airway administration of adenovirus or adenovirus vectors results in a dose-dependent inflammatory response which limits the duration of transgene expression. We explored the possibility that adenovirus infection triggers signal transduction pathways that induce the synthesis of cytokines and thus contribute to the early inflammatory response. Since stimulation of the Raf/mitogen-activated protein kinase (MAPK) pathway activates transcription factors that control the expression of inflammatory cytokines, we examined the activation of this pathway following adenovirus infection. Adenovirus infection induced the rapid activation of Raf-1 and a transient increase in the tyrosine phosphorylation and activation of p42mapk at early times postinfection. Activation of the Raf/MAPK pathway by adenovirus is likely triggered by the infection process, since it occurred rapidly and with various mutant adenoviruses and adenovirus vectors. Moreover, interleukin-8 (IL-8) mRNA accumulation was evident at 20 min postinfection and was induced even in the presence of cycloheximide. Both MAPK activation and IL-8 production were inhibited by forskolin, a potent inhibitor of Raf-1. These results suggest that adenovirus-induced Raf/MAPK activation contributes to IL-8 production. Adenovirus-induced activation of the Raf/MAPK signaling pathway and IL-8 production may play critical roles in the inflammation observed following in vivo administration of adenovirus vectors for gene therapy.

Adenoviruses, Human↗
PubMed2003

Disruption of 3D tissue integrity facilitates adenovirus infection by deregulating the coxsackievirus and adenovirus receptor.

The human coxsackievirus and adenovirus receptor (CAR) represents the primary cellular site of adenovirus attachment during infection. An understanding of the mechanisms regulating its expression could contribute to improving efficacy and safety of adenovirus-based therapies. We characterized regulation of CAR expression in a 3D cell culture model of human breast cancer progression, which mimics aspects of the physiological tissue context in vitro. Phenotypically normal breast epithelial cells (S1) and their malignant derivative (T4-2 cells) were grown either on tissue culture plastic (2D) or 3D cultures in basement membrane matrix. S1 cells grown in 3D showed low levels of CAR, which was expressed mainly at cell-cell junctions. In contrast, T4-2 cells expressed high levels of CAR, which was mainly in the cytoplasm. When signaling through the epidermal growth factor receptor was inhibited in T4-2 cells, cells reverted to a normal phenotype, CAR protein expression was significantly reduced, and the protein relocalized to cell-cell junctions. Growth of S1 cells as 2D cultures or in 3D in collagen-I, a nonphysiological microenvironment for these cells, led to up-regulation of CAR to levels similar to those in T4-2 cells, independently of cellular growth rates. Thus, expression of CAR depends on the integrity and polarity of the 3D organization of epithelial cells. Disruption of this organization by changes in the microenvironment, including malignant transformation, leads to up-regulation of CAR, thus enhancing the cell's susceptibility to adenovirus infection.

Base Sequence↗
PubMed2006

Antiviral therapy for adenovirus infections.

The treatment of severe adenovirus keratoconjunctivitis and life-threatening adenovirus infections in immunocompromised patients is still unsatisfactory. We here review the mode of action and antiviral data for cidofovir and ribavirin, obtained in cell culture, animal models or patients. Several nucleoside or nucleotide analogues have been described that target the adenovirus polymerase, whereas other antiviral targets have been poorly investigated. Furthermore, optimal therapeutic response may be achieved by combining antiviral therapy with immunotherapeutic approaches, as currently being explored.

Adenovirus Infections, Human↗