Ursula Wegner

Adenovirus-receptor interaction with human lymphocytes

Lymphocytes play a key role in cell‐mediated immunity and are host cells for several viral and bacterial pathogens. Their importance in adenovirus (Ad) infections is not yet fully understood. The initial event, the attachment of Ad to lymphocytes and their subsets, was examined using flow cytometry. The study included analysis of stimulated T cells in binding assays with FITC‐labeled Ad fiber. The results confirm that native peripheral lymphocytes express very small amounts of Ad receptors. Stimulation with PHA and interleukin 2 induced the expression. The presence of Ad DNA as a sign of internalization in stimulated cells was demonstrated using the polymerase chain reaction. The findings suggest that lymphocytes after stimulation can turn into target cells for Ad. This is particularly important if there are indications for persistence of Ad, and in the case of immunocompromised patients severe, life‐threatening diseases can develop. J. Med. Virol. 51:252–257, 1997.

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level

Abstract Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3′-fluorothymidine triphosphate (IC50 0.63 μM), 2′,3′-dideoxy-3′-fluoroguanosine triphosphate (IC50 0.71 μM) and 2′,3′-dideoxy-3′-fluorouridine triphosphate (IC50 2.96 μM). The most efficient 2′,3′-dideoxynucleoside triphosphates were 2′,3′-dideoxycytidine triphosphate (ddCTP; IC50 1.0 μM), 2′,3′-dideoxyadenosine triphosphate (IC50 1.6 μM) and 2′,3′-dideoxythymidine triphosphate (IC50 1.82 μM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3′-fluorothymidine and 2′,3′-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity.

Fluorescent focus reduction assay for the screening of antiadenoviral agents

A method for screening of antiviral compounds against adenoviruses was established. Test compounds were diluted and plated in chamber slides for tissue culture. Drug-treated, virus-infected cultures were stained with fluorescein isothiocyanate conjugated rabbit antibodies against adenovirus hexon type 2 and fluorescent cells were counted by microscopy. This assay is more sensitive than the colorimetric method and requires smaller volumes of compounds when compared with the standard method using plaque assay.

Molecular and clinical characteristics of respiratory syncytial virus infections in hospitalized children

The objective of this study was to determine the importance of respiratory syncytial virus (RSV) for hospitalization in the north east of Germany and to obtain molecular epidemiological data of the circulating strains. Using a rapid and sensitive reverse transcriptase-PCR, it was found that a quarter of pediatric respiratory disease admissions were due to RSV. Infections caused by RSV in hospitalized patients were determined over the whole year. Both RSV groups A and B were identified with a predominance of RSV A (86%) over the entire period. The analysis of the deduced amino acid sequences by direct sequencing showed that very similar RSV strains are circulating in the community.

Analysis of genotypes of human astrovirus isolates from hospitalized children in Northeastern Germany.

disease, which was likely responsible for the initial hematogenic spread and seeding of the organism. Rothia dentocariosa is usually susceptible to several antibiotics, and penicillin plus an aminoglycoside during the first 2 weeks of treatment has been the most frequent antibiotic regimen used in patients with endocarditis [7, 8]. Although uncommon, Rothia dentocariosa should be regarded as a potential cause of vertebral osteomyelitis.