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PubMed1992

Epidemiology of enteric adenovirus infection in prospectively monitored Argentine families.

To examine the role of enteric adenoviruses (EAV) in an urban area of Buenos Aires (Argentina), we prospectively studied faecal samples from 49 families of newborns. These were monitored weekly for diarrhoea for 2 years. A total of 180 samples from cases of diarrhoea and 766 samples obtained during diarrhoea-free periods were studied by dot-blot hybridization with an EAV-specific DNA probe. EAV were found in 6/180 (3.3%) cases of diarrhoea and 6/766 (0.8%) asymptomatic samples (P < 0.015). Incidence of EAV was 3.9 cases per 100 person-years in children < 60 months old. EAV-related diarrhoeas were slight and of short duration. In addition, 129 faeces from hospital out-patients, 1-30 months old, were also studied. EAV was identified in 7/129 cases (5.4%). These cases were 9.5 +/- 3.5 months old and the diarrhoea was mild or severe, of 3 +/- 1.5 days of duration. We suggest that EAV are low-risk causes of diarrhoea under natural conditions, although a few children may develop more severe diarrhoea. The diagnosis of EAV needs to be considered in these patients.

Adenovirus Infections, Human↗
PubMed1999

Retargeting to EGFR enhances adenovirus infection efficiency of squamous cell carcinoma.

BACKGROUND: Adenovirus-mediated gene therapy has been used for squamous cell carcinoma of the head and neck (SCCHN), but the in vivo efficacy has been limited by a lack of tissue specificity and low infection efficiency. We are interested in improving cancer gene therapy strategies using targeted adenovirus vectors. OBJECTIVE: To determine if the infection efficiency of adenovirus-mediated gene transfer to SCCHN cells could be enhanced by retargeting to the epidermal growth factor receptor (EGFR), which is known to be overexpressed in these tumors. DESIGN: Epidermal growth factor receptor retargeting in SCCHN cells was accomplished with a bispecific antibody that recognized the knob domain of adenovirus as well as EGFR. Using this retargeting schema, we compared the infection efficiency and specificity of unmodified and EGFR-retargeted adenovirus. RESULTS: Squamous cell carcinoma of the head and neck cell lines were shown to be infected by adenovirus with low efficiency, which is likely because of the low level of adenovirus receptor expressed in the SCCHN cells. Epidermal growth factor receptor retargeting markedly enhanced transduction in both SCCHN cell lines and primary tumor tissue, as indicated by the elevated levels of reporter gene expression. Furthermore, retargeting enhanced infection of tumor tissue compared with normal tissue from the same patient. CONCLUSIONS: Epidermal growth factor receptor retargeting enhanced adenovirus infection of SCCHN cells and, in doing so, augments the potency of the vector. This modification makes the vector potentially more valuable in the clinical setting.

Adenoviridae↗
PubMed1989

Prosomes discriminate between mRNA of adenovirus-infected and uninfected HeLa cells.

Prosomes are small cytoplasmic RNP complexes associated with repressed mRNA. In in vitro translation, they discriminate between the mRNA of adenovirus-infected HeLa cells and those of uninfected cells grown under normal conditions. Prosomes as well as their RNA constituents interact much more strongly with poly(A)+ mRNA of infected cells and inhibit their translation in vitro preferentially. A possible role of prosomes in the differential regulation of translation is discussed.

Adenoviridae↗
PubMed1985

Bronchiolitis obliterans and pneumonia induced in young dogs by experimental adenovirus infection.

Young beagle dogs were experimentally inoculated with canine adenovirus Type 2 and studied by virologic, histologic, immunoperoxidase, and ultrastructural methods from 1 to 26 days after inoculation. Virus was recovered from lungs at 2, 3, 5, and 8 days after inoculation. Virions and viral antigen were demonstrated by ultrastructural and immunoperoxidase techniques in nonciliated bronchiolar epithelial cells and mucous cells in bronchioles, bronchi, and trachea as well as in bronchial and tracheal submucosal gland epithelial cells. Viral replication in airways was associated with a severe necrotizing and proliferative bronchitis and bronchiolitis. Virus and viral antigen were demonstrated in Type 2 alveolar epithelial cells and were associated with interstitial pneumonia. Partial and complete stenosis of bronchioles by connective tissue was observed at 15 and 26 days after inoculation. There was a 50% reduction (P less than 0.02) in mean terminal bronchiolar cross-sectional area in the right middle lobe of virus-infected dogs at 26 days after inoculation. It is concluded that experimental adenovirus infection in dogs induces bronchiolitis obliterans and that this experimental model may be useful for studies on adenovirus-induced lung injury during early life.

Adenoviridae Infections↗
PubMed1995

Adenovirus infection induces rearrangements in the intranuclear distribution of the nuclear body-associated PML protein.

We have studied at the ultrastructural level the localization of PML protein in response to adenovirus infection in HeLa cells. In nuclei of noninfected cells or at the early stage of infection, PML accumulated at the border of nuclear bodies as previously described [Koken et al. (1994) EMBO J. 13, 1073-1083]. Interestingly, we demonstrate herein that PML is also a component of the interchromatin granule-associated zones, recently described structures containing U1 snRNP [Visa et al. (1993) Eur. J. Cell Biol. 60, 308-321], suggesting that PML protein might be involved in some steps of splicing events. However, as the infection progressed these two cellular PML-containing structures disappeared but significant amounts of PML accumulated within two virus-induced structures, essentially the clear amorphous inclusions, but also the protein crystals. Relocalization of this protein to virus-induced structures may reflect an inactivation of PML functions.

Adenoviruses, Human↗
PubMed1975

Animal DNA-dependent RNA polymerases. Partial purification and properties of three classes of RNA polymerases from uninfected and adenovirus-infected HeLa cells.

DNA-dependent RNA polymerase was solubilized from normal and adenovirus-2 infected HeLa cells. Multiple peaks of enzyme activity were separated by DEAE-Sephadex chromatography. In addition to class A and B enzyme activities (respectively insensitive and sensitive to inhibition by 10 nM alpha-amanitin), three peaks of class C enzyme activity were found which are sensitive to inhibition by alpha-amanitin only at much higher concentrations (0.1 mM). Rechromatography of these class C peaks indicates that they are not chromatographic artifacts. Class C enzymes differ from class A and B enzymes by several criteria including inhibition by alpha-amanitin, immunological properties, and the ability to transcribe native calf thymus DNA at high ionic strength. However, the ionic strength optimum and the divalent cation requirements of class C enzymes are not invariant characteristics of the enzymes and are markedly dependent on the nature and the amount of template in the reaction. No differences, either qualitative or quantitative, were found between the multiple enzymes isolated from normal or adenovirus-2 infected cells. All of the partially purified HeLa cell RNA polymerases were able to transcribe an intact double-stranded adenovirus-2 DNA under conditions where no transcription occurred with purified calf thymus AI and B RNA polymerases. Since the multiple enzymes were devoid of endonuclease and exonuclease activities, the ability of the partially purified enzymes to transcribe adenovirus-2 DNA cannot be ascribed to initiation of RNA synthesis at nicks of single-stranded regions of the DNA. No differences in transcriptional ability between corresponding enzyme classes from normal or infected cells, but a comparison of the ability of the various enzyme classes to transcribe intact viral DNA revealed large differences. Although partially purified HeLa class A and B enzymes were able to initiate on the intact viral DNA to a limited extent only, it appears that the class C enzymes transcribe intact duplex DNA much more efficiently than any other class of eukaryotic polymerase yet reported.

Adenoviridae↗
PubMed1983

A naturally occurring intestinal mouse adenovirus infection associated with negative serologic findings.

Large basophilic intranuclear inclusions were observed in the intestinal epithelium of clinically normal mice. Electron micrographs of the inclusions showed them to be caused by an adenovirus, even though serological testing for mouse adenoviruses in a complement fixation test using the FL strain of mouse adenovirus yielded no titers. A diagnosis of an adenovirus infection resembling that caused by the K87 strain was made.

Adenoviridae Infections↗
PubMed1996

Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo.

Human adenoviruses have been developed as an attractive vehicle for in vivo liver-directed gene therapy. Problems with the application of first generation recombinant adenoviruses to liver-directed gene therapy have been transient expression of the recombinant gene and development of hepatitis. Previous studies in mouse models of gene transfer to liver and lung suggested that MHC class I-restricted cytotoxic T lymphocytes (CTLs) to viral antigens may be effectors in the elimination of transgene expression. The goal of this study was to evaluate the importance of viral antigens versus transgene product in inducing CTL mediated hepatocyte destruction in vivo. Immunization of C57BL/6 mice with a lacZ-expressing adenovirus elicited CTL responses to both viral antigens and the transgene product, beta-galactosidase (beta-gal). Adoptive transfer experiments, as well as studies involving lacZ-transgenic mice (ROSA-26) revealed that CTLs to viral antigens are sufficient to destroy virus-infected hepatocytes, indicating that CTLs to beta-gal can not solely account for the observed hepatocyte destruction that has characterized the use of first generation viruses. In addition, we confirmed that B cell-mediated events do not participate in destruction of hepatocytes in vivo, despite the production of virus- and beta-gal-specific antibodies. These data confirm the hypothesis that viral gene expression elicits host responses that contribute to the problem of transgene instability. Recombinant adenoviruses must be redesigned to diminish viral gene expression if they are to be used in the treatment of chronic diseases.

Adenoviruses, Human↗
PubMed1991

Adenovirus infection of the kidney: mass formation in a patient with Hodgkin's disease.

Adenovirus (AV) infection usually has a benign course in normal hosts; however, in immunocompromised patients, AV may cause pneumonia, cystitis, or disseminated disease with substantial morbidity and even mortality. Although pulmonic AV involvement is common, infection of the kidney is unusual. The histologic findings previously described include tubular necrosis with interstitial inflammation and glomerulonephritis. We report a case of an AV-induced unilateral mass lesion in the kidney of a patient with Hodgkin's disease (HD) following bone marrow transplantation.

Adenovirus Infections, Human↗
PubMed1999

Fulminant hepatic failure caused by adenovirus infection following bone marrow transplantation for Hodgkin's disease.

Adenoviruses are increasingly realised to be responsible for serious morbidity and mortality following allogeneic bone marrow transplantation. We describe a case of fulminant hepatic failure due to adenovirus serotype 2 in a 39-year-old woman who received a matched sibling allogeneic bone marrow transplant for multiply relapsed Hodgkin's disease. Isolated fulminant hepatic failure caused by this serotype of adenovirus has not previously been described.

Adenoviridae Infections↗