Antiviral and immunomodulatory activity of the metal chelator ethylenediaminedisuccinic acid against cytomegalovirus in vitro and in vivo.

Antiviral activity of the metal chelator ethylenediaminedisuccinic acid (EDDS) was examined in vitro against human cytomegalovirus (HCMV) wild type strains and strains that are resistant against ganciclovir (GCV) and cidofovir (HPMPC). EDDS inhibited the replication of wild-type as well as GCV- and HPMPC-resistant strains with a 50% effective concentration of 7.4-12 microg/ml.

Polyomavirus viruria in bone marrow transplant recipients: lack of correlation with clinical symptoms.

Background: Human polyomavirus (HPV) infection is controversially discussed as a factor influencing the outcome of bone marrow transplantation (BMT).

Patients And Methods: Here we report on 62 patients undergoing BMT with clinical signs of urocystitis, such as micro- or macrohematuria with more or less severe dysuria. These patients were tested for the presence of HPV in urine specimens (n = 80) by transmission electron microscopy (TEM).

Cross-reactivity in flavivirus serology: new implications of an old finding?

To investigate the influence of pre-existing antibodies against tick-borne encephalitis (TBE) or yellow fever (YF) viruses on dengue virus antibody test results, we examined sera from vaccinees and from individuals with previous TBE virus infection. Distinct IgG antibody cross-reactivity was found in about 15.1% in the YF-vaccinated group and in about 9.

Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am Main area, Germany.

Herpes simplex virus (HSV) types 1 and 2 are widespread human infectious agents that are responsible for persistent and latent infections. HSV type 2 (HSV-2) infection is usually transmitted sexually, while HSV type I (HSV-1) is commonly acquired by saliva contact during childhood. In a retrospective study, sera from more than 4,800 patients were analyzed for HSV type-specific IgG antibodies.

Docking studies reveal a selective binding of D-penicillamine to the transactivator protein of human immunodeficiency virus type 1.

DOCK and Affinity studies were carried out to study the binding of D- and L-penicillamine to the transactivator protein (tat) of human immunodeficiency virus type 1 (HIV-1). These studies reveal a selective binding of D-penicillamine to the cysteine-rich region covering amino acid residues 20-38 of the tat protein. A careful analysis of the components of the binding energy of the D- and L-isomers reveals that the D-isomer has a more favorable van der Waals interaction resulting from an optimal placement of the dimethylthiomethyl side chain in the binding site.

Evaluation of a new combined antigen and antibody human immunodeficiency virus screening assay, VIDAS HIV DUO Ultra.

Combined antigen and antibody screening (fourth-generation) assays reduce the diagnostic window period between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis by 4 days, on average, in comparison to antibody-only (third generation) enzyme immunoassays (EIAs). The aim of the present study was to assess whether the new VIDAS HIV DUO Ultra (Biomérieux, Marcy-l'Etoile, France) showed an improved sensitivity and specificity in comparison to licensed fourth-generation assays. A total of 16 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 257 potentially cross-reactive serum samples were tested with VIDAS DUO HIV Ultra, Genscreen Plus HIV Ag-Ab, Enzygnost HIV Integral, Enzymun-Test HIV Combi, Genscreen HIV 1/2, version 2 (third-generation EIA), and Genetic Systems HIV-1 Ag EIA (p24 antigen assay).

Performance characteristics of an automated PCR assay for the quantification of cytomegalovirus DNA in plasma.

The COBAS Amplicor CMV Monitor test (Roche Diagnostics), an automated polymerase chain reaction (PCR) assay for the quantification of cytomegalovirus (CMV) DNA in plasma samples, was evaluated in a routine diagnostic laboratory. Using cell culture-derived CMV and CMV-negative human plasma, the linear detection range of the assay as well as its intra-and inter-assay variabilities were assessed. The study design allowed distinguishing variations in results related to amplification and detection from those caused by differences in the efficiency of DNA extraction.

Evaluation of the new LCx HIV RNA quantitative assay: comparison with the Cobas Amplicor HIV Monitor assay.

In the present study we evaluated the performance of the new LCx HIV RNA quantitative kit (Abbott Laboratories, Delkenheim, Germany) for the quantitative detection of HIV-1 RNA in human plasma in comparison to the Cobas Amplicor HIV-1 Monitor assay (Roche Diagnostics, Branchburg, N.J.), including samples containing a variety of HIV-1 subtypes.

Kaposi's sarcoma-associated herpesvirus seroprevalence in selected german patients: evaluation by different test systems.

A total of 603 serum samples obtained from 12 different patient and control groups, including potentially cross-reactive sera, were tested for the presence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8). The assays used were an inhouse immunofluorescence test (IFT) employing latent KSHV antigens and a prototype enzyme-linked immunosorbent assay (ELISA) coated with recombinant latency-associated KSHV nuclear antigen (LANA, open reading frame 73) and the K8.1 protein.

S-acyl-2-thioethyl (SATE) pronucleotides are potent inhibitors of HIV-1 replication in T-lymphoid cells cross-resistant to deoxycytidine and thymidine analogs.

The biological evaluation of mononucleotide prodrugs (pronucleotides) of various nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine (AZT), zalcitabine (ddC) and lamivudine (3TC) was reported in human T-lymphoid MOLT-4/8 cells which were grown continuously for more than 1 year in a medium containing cytarabine (Ara-C). In this cell line, expression of deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) was decreased in comparison to parental cells (3.8 and 2.

[Epidemiological analysis of immunity against vaccine-preventable diseases: rubella, measles, mumps and chickenpox].

Background And Objective: Measles, mumps, rubella and varicella zoster virus (VZV) infections are regarded as typical diseases of childhood: They are normally clinically mild and result in lifelong immunity. Severe clinical disease is known in immunocompromised patients; rubella virus infections during pregnancy often result in congenital rubella syndrome. All these diseases are preventable by vaccination which is recommended in Germany, recently vaccination against VZV for teenager without immunity since July 2001.

Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals.

Background: Relatively little is known about the long-term durability of viral suppression in individuals initially achieving a viral load of less than 50 copies/ml within 24 weeks of starting antiretroviral therapy, nor the extent to which therapy interruption accounts for the loss of suppression.

Methods: We intensely followed all 336 antiretroviral-naive patients attending the Goethe Universitat Clinic who began multi-drug combination regimens and in whom a viral load of less than 50 copies/ml was achieved within 24 weeks, in order to assess the risk of viral load rebound. Inspection of case notes allowed the distinction of viral rebound according to whether there was an associated complete interruption of therapy.

[Atypical herpes simplex virus type 2 manifestations on the hand].

Cutaneous and mucocutaneous herpes simplex virus (HSV) type 1 and type 2 infections are some of the most common virus infections of man. Despite optimal laboratory diagnosis and widely improved antiviral therapy, only 20 percent of patients suffering from genital herpes are correctly diagnosed, and even less often is appropriate therapy prescribed. Atypical herpes includes vegetating forms in atypical locations, mild cases and even asymptomatic herpes.

Zidovudine (AZT) resistance in H9 cells due to decreased TK expression is associated with hypermethylation of TK gene.

AZT resistant human T-lymphoid H9 cells, deficient in TK gene expression, re-expressed TK mRNA and regained the ability to metabolize AZT by exposure to the demethylation agent azacytidine (AzaCd). Cytotoxic and anti-HIV-1 effects of AZT were increased in H9 AZT resistant cells treated with AzaCd when compared to untreated cells. This leads to the assumption that drug induced DNA hypermethylation was involved in the TK gene-silencing mechanism.

Cytarabine treatment of human T-lymphoid cells induces decreased HIV-1 receptor expression and reduced HIV-1 susceptibility.

Continuous cultivation of T-lymphoid C8166 cells in the presence of pharmacological relevant concentration of cytarabine (Ara-C) results in significantly decreased expression of CD4 and CXCR4 molecules, the major cellular receptor and co-receptor of T-lymphotropic HIV-1 isolates. This change in receptor expression leads to decreased susceptibility of Ara-C resistant cells to HIV-1 infection demonstrated by reduced binding and penetration of HI-virus.

Antisense oligonucleotide ISIS 2922 targets IE-expression and prevents HCMV-IE-induced suppression of TSP-1 and TSP-2 expression.

ISIS 2922, but not ganciclovir (GCV), inhibits HCMV immediate early protein (IE) expression in different infected cell lines and prevents down-modulation of extracellular matrix proteins thrombospondin-1 and -2 induced by IE proteins. While action of ISIS 2922 is mainly due to specific inhibition of IE 2 mRNA, there is also evidence for unspecific effects in terms of inhibition of virus adhesion and penetration.

An epidemiological study of HIV-infections in Frankfurt/Main and other major cities in Germany.

Epidemiological studies can help to understand the effects of medical treatment of HIV infections. Accordingly, this study was designed to discuss the most important parameters in Frankfurt/Main and other big German cities from 1984 to 2000. The number of HIV tests performed by Frankfurt's Virology has been decreasing continually since 1991.

[Study of vaccination for travel shows: serious gaps in polio, diphtheria and tetanus vaccination].

In a retrospective study, we analyzed the immune status of 1134 travellers (621 males, 513 females), by comparing actual with recommended vaccinations, in particular with regard to malaria. 61.6% of travellers showed complete immunization against diphtheria, 73.

Diagnostics and treatment of HIV-discordant couples who wish to have children.

Over the last years the reality surrounding HIV-infection has undergone a considerable change with regard to the life expectancy of patients, and the plans they can make for their lives. Because the majority of the HIV positive population is of reproductive age, one of these plans might be to have children, often as an expression of a fulfilled partnership. The need for medical support to realize this wish, however, is often confronted with ethical, medical or forensic restraints.

Human cytomegalovirus circumvents NF-kappa B dependence in retinal pigment epithelial cells.

The human CMV (HCMV) is a persistent virus that may cause severe inflammatory responses especially in immunocompromised hosts. In different cell types, HCMV infection leads to the activation of the pleiotropic transcription factor, NF-kappaB, which triggers virus replication but also propagates cell-mediated inflammatory mechanisms that largely depend on PG synthesis. We investigated the interactions of HCMV and the NF-kappaB-dependent PG synthesis pathway in cultures of retinal pigment epithelial (RPE) cells that are known to be infected in HCMV retinitis patients.

Enterovirus infections in Germany: comparative evaluation of different laboratory diagnostic methods.

Background: The diagnosis of an enterovirus infection may be achieved through direct virus detection from fecal or cerebrospinal fluid (CSF) samples by virus isolation or PCR. Serologically, a significant rise in antibody titer may be detected and different enteroviral types can be differentiated using the neutralization assay.

Patients And Methods: We investigated the contribution of these different laboratory parameters to the diagnosis of enterovirus infections occurring in the Frankfurt am Main area during the years 1997 to 1999, including an echovirus 30 outbreak in a group of children with aseptic meningitis in 1997.

Inhibition of cytomegalovirus immediate early gene expression: a therapeutic option?

The replication cycle of the human cytomegalovirus (HCMV) is characterized by the expression of immediate early (IE), early (E), and late (L) gene regions. Current antiviral strategies are directed against the viral DNA polymerase expressed during the early phase of infection. The regulation of the IE-1 and IE-2 gene expression is the key to latency and active replication due to their transactivating and repressing functions.

Hepatitis B virus markers in anti-HBc only positive individuals.

Isolated reactivity to hepatitis B virus (HBV) core antigen (anti-HBc) is observed relatively frequently in immunocompromised individuals, intravenous drug abusers (IVDA), and in the presence of HCV infection. The reason for the lack of HBsAg is not clear. The aim of the present study was to investigate which factors (genetic variability of S gene, low-level HBsAg, and immune complexes may be responsible for the failure of HBsAg detection with commercial HBsAg screening assays.