Macaca arctoides gammaherpesvirus 1 (strain herpesvirus Macaca arctoides): virus sequence, phylogeny and characterisation of virus-transformed macaque and rabbit cell lines.

Herpesvirus Macaca arctoides (HVMA) has the propensity to transform macaque lymphocytes to lymphoblastoid cells (MAL-1). Inoculation of rabbits with cell-free virus-containing supernatant resulted in the development of malignant lymphomas and allowed isolation of immortalised HVMA-transformed rabbit lymphocytes (HTRL). In this study, the HVMA genome sequence (approx.

Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD.

Purpose: Rabbit antithymocyte globulin (ATG) is commonly used before allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent graft-versus-host disease. Studies comparing the effect of different ATG preparations and dosages on immune reconstitution and risk for Epstein-Barr virus (EBV)-mediated post-transplant lymphoproliferative disorder (PTLD) are rare.

Methods: In this retrospective study, we determined T and B cell subsets by flow cytometry after allo-HSCT in children, who received ATG-Genzyme (ATG-G, n = 15), ATG-Fresenius (ATG-F, n = 25) or no-ATG treatment (n = 19).

Simvastatin treatment showed no prophylactic effect in influenza virus-infected mice.

Simvastatin, a cholesterol-lowering drug, is reported to have immunomodulatory properties that attenuated acute lung injury independent of their major lipid lowering effects. Based on these reports, simvastatin is expected to be used for influenza prophylaxis and treatment. The present study evaluated the efficacy of simvastatin against influenza A/PR/8/34 virus infection in a murine model.

Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

Infants with severe primary combined immunodeficiency (SCID) and children post-allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period.

Hemophagocytic syndrome caused by primary herpes simplex virus 1 infection: report of a first case.

Introduction: Hemophagocytic syndrome represents a severe hyperinflammatory condition by activated macrophages. Leading viral triggering agents are Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus.

Materials And Methods: We present a patient with Wegener's granulomatosis on azathioprine and prednisone medication, who developed a life-threatening hemophagocytic syndrome.

Chronic norovirus infection after kidney transplantation: molecular evidence for immune-driven viral evolution.

Background: Norovirus infection is the most common cause of acute self-limiting gastroenteritis. Only 3 cases of chronic norovirus infection in adult solid organ transplant recipients have been reported thus far.

Methods: This case series describes 9 consecutive kidney allograft recipients with chronic norovirus infection with persistent virus shedding and intermittent diarrhea for a duration of 97-898 days.

Monitoring of Epstein-Barr virus load after hematopoietic stem cell transplantation for early intervention in post-transplant lymphoproliferative disease.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease is a life-threatening complication following hematopoietic stem cell transplantation. A quantitative polymerase chain reaction to evaluate EBV-genome copy numbers based on a nested polymerase chain reaction and an end-point dilution was used. Applying this assay EBV load was prospectively screened weekly in 123 patients after transplantation.

Antiviral activity of cyclosaligenyl prodrugs of the nucleoside analogue bromovinyldeoxyuridine against herpes viruses.

A series of 42 lipophilic bromovinyldeoxyuridine monophosphates (BVDUMPs) are presented as potential prodrugs of the antiviral agent (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU). The 5'-cycloSal-masking group technique has been applied to this cyclic nucleoside analogue to achieve delivery of the monophosphate of BVDU inside the target cells. The new substances have been tested for their antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), thymidine kinase-deficient (TK(-)) HSV-1, varicella-zoster virus (VZV), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV).

Comparison of a LightCycler-based real-time PCR for quantitation of Epstein-Barr viral load in different clinical specimens with semiquantitative PCR.

Measurement of viral load is important in predicting and monitoring of Epstein-Barr virus (EBV)-associated diseases especially in immunocompromised patients. The objectives of this study were the development of a LightCycler-based real-time PCR assay using primers and probes which recognize the virus capsid antigen p23-encoding region and its comparison to the semiquantitative PCR. The LightCycler protocol shows a high degree of specificity and inter- and intra-assay reproducibility.

Inhibitory efficacy of cyclosal-nucleoside monophosphates of aciclovir and brivudin on DNA synthesis of orthopoxvi ruses.

Previous studies have shown that cycloSaligenyl-monophosphate (cycloSal-MP) derivatives of aciclovir (ACV), penciclovir (PCV) and brivudin (BVDU) can act as inhibitors of vaccinia virus and cowpox virus replication in vitro. The aim of the present study was to evaluate the inhibatory efficacy on DNA synthesis in vaccinia and cowpox viruses of several cycloSal-pro-nucleotides of ACV and BVDU, which have proven activity against pox viruses. Viral DNA was quantified in treated and non-treated virus-infected cells by semi-quantitative PCR on the basis of the haemagglutinin protein gene of orthopoxviruses.

Fatal outcome of herpes simplex virus type 1-induced necrotic hepatitis in a neonate.

In neonates, herpes simplex virus (HSV) infections can lead to severe diseases associated with high mortality. We report a 6-day-old girl who developed clinical signs of fulminant hepatic failure accompanied by infectious-toxic shock and disseminated coagulopathy secondary to HSV type 1 (HSV-1) infection. The diagnosis was performed postmortem by demonstration of HSV-1 DNA in liver tissue as well as by retrospective detection of HSV-specific antibodies.

In vitro activity of cycloSal-nucleoside monophosphates and polyhydroxycarboxylates against orthopoxviruses.

Because variola virus might be used as a pathogen in biological attacks, there is an urgent need to provide effective antiviral drugs for the treatment of orthopoxvirus infections. Thus, the aim of the present study was to test the antiviral activity of 3 pro-nucleotides of the acyclic nucleoside analogues aciclovir (ACV), 3 of penciclovir (PCV) and 38 of the cyclic nucleoside analogue brivudin (BVDU), on the basis of cycloSaligenyl-nucleoside monophosphate approach against vaccinia virus and cowpox virus in vitro. In further experiments, 13 synthetic humic acid-like polymers, so-called polyhydroxycarboxylates, were examined.

Transformation of rabbit lymphocytes by an Epstein-Barr virus-related herpesvirus from Macaca arctoides.

Herpesvirus Macaca arctoides (HVMA), an Epstein-Barr virus (EBV)-related herpesvirus of macaque origin, induces malignant lymphomas in rabbits. To get more insights into the oncogenesis of the EBV/HVMA infection the aim of the present study was to prove the in vitro transforming ability of HVMA for rabbit lymphocytes as well as human umbilical cord blood lymphocytes. As a result, B-cell transformation could be demonstrated after infection with HVMA in all mononuclear cell samples of 20 rabbits.

Recent developments in the prevention and treatment of Epstein-Barr virus-associated lymphoproliferative diseases.

Epstein-Barr virus (EBV) infection and its relevance in post-transplant lymphoproliferative diseases (PTLDs) is an increasing area of concern. PTLD can differ clinically from a mononucleosis-like syndrome to malignant lymphoma. The incidence varies between < 1 and > 20% depending on different risk factors and the kind of transplant.

Cyclosal-pronucleotides--development of first and second generation chemical trojan horses for antiviral chemotherapy.

Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogs against different viral diseases. Moreover, pronucleotides are valuable tools for studies concerning the nucleoside/nucleotide metabolism. The basic idea is to achieve nucleotide delivery into cells, bypassing limitations with intracellular formation of nucleotides from their nucleoside precursors.

Establishment and cidofovir sensitivity of a cell line from a heart transplant recipient with multiple cutaneous tumors.

A new cell line, designated as Tuwei00, is described. It originated from an Epstein-Barr virus-positive skin tumor biopsy of a heart transplant recipient, whose numerous cutaneous neoplasms were treated with the antiviral drug cidofovir what caused at least transient remissions. The cell line was established in vitro and maintained for more than 70 passages.

Binding of a N,N'-bisheteryl derivative of dispirotripiperazine to heparan sulfate residues on the cell surface specifically prevents infection of viruses from different families.

N,N'-bisheteryl derivatives of dispirotripiperazine (DSTP) are a novel class of antiviral compounds with some of their representatives very effectively inhibiting the replication of herpes simplex virus type 1 (HSV-1) in cell culture. Using one representative of these compounds, the N,N'-bis(1-oxido[1,2,5]oxadiazolo[3,4-d]pyrimidin-7-yl)-3,12-diaza-6,9-diazonia(5,2,5,2)dispirohexadecane dichloride (DSTP 27), we here further tried to elucidate the molecular mechanisms responsible for the antiviral activity. The results from plaque reduction assays under a variety of conditions suggest that inhibition of HSV-1 strain Kupka replication by DSTP 27 occurs at the level of viral attachment by blockade of heparan sulfate (HS) structures on the cell surface that are used as viral receptors.

Pre-emptive therapy with rituximab for prevention of Epstein-Barr virus-associated lymphoproliferative disease after hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Therefore, early diagnosis of EBV reactivation and pre-emptive therapy may be clinically useful. We report three patients who presented with an extremely high EBV load in peripheral blood mononuclear cells and plasma without evidence of EBV disease.

The therapy of virus-associated epithelial tumors of the face and the lips in organ transplant recipients.

The risk of developing malignant cutaneous neoplasms is increased after organ transplantation. We report three patients with malignant tumors of the epithelium of the facial skin and the lips after kidney and heart transplantation, respectively. They showed an aggressive course of the disease with more than five synchronous or metachronous basal cell and squamous cell carcinomas.

CycloSal-BVDUMP pronucleotides: how to convert an antiviral-inactive nucleoside analogue into a bioactive compound against EBV.

Novel cycloSal-BVDUMP triesters 2-4 5-[(E)-2-bromovinyl]-2'-deoxyuridine (BVDU, 1) have been studied with regard to their potential anti-EBV activity. In addition to the 3'-unmodified cycloSal-BVDUMP triesters 2a-f, the 3'-hydroxyl function has been esterified with different aliphatic carboxylic acids (3a-g) and alpha-amino acids having natural and nonnatural Calpha-configuration (4a-m). In addition to the synthesis of these compounds, different physicochemical properties of the new derivatives will be reported, i.

In vitro activity of polyhydroxycarboxylates against herpesviruses and HIV.

The antiviral activity of 17 polyhydroxycarboxylates derived from phenolic compounds was evaluated against herpesviruses and HIV. When present during virus adsorption several of the polymers exhibited potent activity against herpes simplex virus type 1 (HSV-1), HSV-2, thymidine kinase deficient HSV-1, human cytomegalovirus (HCMV) and HIV-1 and HIV-2 at concentrations that were not toxic to the host cells. A close correlation was found between the 50% inhibitory concentrations of the polyhydroxycarboxylates against HCMV-induced cytopathicity, their inhibitory effect on the expression of HCMV-specific immediate early antigens and their inhibitory effects on HCMV adsorption to the cells.

Synthesis, hydrolysis and anti-EBV activity of a series of 3'-modified cycloSal-BVDUMP pronucleotides.

A series of cycloSal-BVDUMP phosphate triesters has been prepared. The prototype compound was 3-methyl-cycloSal-BVDUMP 2. Furthermore, a series of 3'-O-acyl-modified derivatives having carboxylic acids with different lipophilicity or a L-configurated alpha-amino acid (phenylalanine) was prepared.

Semiquantitative PCR analysis of Epstein-Barr virus DNA in clinical samples of patients with EBV-associated diseases.

The laboratory diagnosis of primary and reactivated Epstein-Barr virus (EBV) infection is based on serologic methods in immunocompetent patients. However, in immunocompromised patients, serologic data are difficult to interpret and do not often correlate with clinical data. In order to find a useful and practical marker for diagnosis of EBV-related diseases, a polymerase chain reaction (PCR) assay was established for semiquantitative detection of EBV sequences.