An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3.

Background: We previously showed that the envelope (env) sequence of a human endogenous retrovirus (HERV)-W locus on chromosome Xq22.3 is transcribed in human peripheral blood mononuclear cells. The env open reading frame (ORF) of this locus is interrupted by a premature stop at codon 39, but otherwise harbors a long ORF for an N-terminally truncated 475 amino acid Env protein, starting at an in-frame ATG at codon 68.

Interaction of human immunodeficiency virus gp120 with the voltage-gated potassium channel BEC1.

Retrovirus replication critically depends on a dynamic interplay between retroviral and host proteins. We report on the binding of the surface subunit (glycoprotein 120 (gp120)) of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) to the cytoplasmic C-terminus of the voltage-gated potassium channel BEC1 (brain-specific ether-a-go-go-like channel 1), an interaction that can result in the repression of BEC's activity and the inhibition of HIV-1 particle-release. BEC1 protein was found to be expressed in T cells and macrophages, the major target cells of HIV-1.

Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger protein and androgen receptor.

More than 2000 human endogenous retrovirus (HERV) sequences are present in the human genome, yet only a few are intact and able to produce proteins. The normal functions of these, if any, are unknown, but some HERV proteins have been implicated in cancers, in particular germ-cell cancers. For instance, it has been documented that (i) patients with germ-cell tumours frequently produce antibodies against HERV proteins; (ii) transgenic mice expressing HERV-K (HML-2) rec are prone to testicular carcinoma in situ; and (iii) Rec can bind and suppress a guardian of germline stem-cell pluripotency, the promyelocytic leukaemia zinc-finger protein (PLZF).

Analysis of transcribed human endogenous retrovirus W env loci clarifies the origin of multiple sclerosis-associated retrovirus env sequences.

Background: Multiple sclerosis-associated retrovirus (MSRV) RNA sequences have been detected in patients with multiple sclerosis (MS) and are related to the multi-copy human endogenous retrovirus family type W (HERV-W). Only one HERV-W locus (ERVWE1) codes for a complete HERV-W Env protein (Syncytin-1). Syncytin-1 and the putative MSRV Env protein have been involved in the pathogenesis of MS.

Human endogenous retrovirus HERV-K(HML-2) encodes a stable signal peptide with biological properties distinct from Rec.

Background: The human endogenous retrovirus HERV-K(HML-2) family is associated with testicular germ cell tumors (GCT). Various HML-2 proviruses encode viral proteins such as Env and Rec.

Results: We describe here that HML-2 Env gives rise to a 13 kDa signal peptide (SP) that harbors a different C-terminus compared to Rec.

Human endogenous retrovirus family HERV-K(HML-2) RNA transcripts are selectively packaged into retroviral particles produced by the human germ cell tumor line Tera-1 and originate mainly from a provirus on chromosome 22q11.21.

The human germ cell tumor line Tera-1 produces retroviral particles which are encoded by the human endogenous retrovirus family HERV-K(HML-2). We show here, by quantitative reverse transcriptase PCR, that HML-2 gag and env RNA transcripts are selectively packaged into Tera-1 retroviral particles, whereas RNAs from cellular housekeeping genes and from other HERV families (HERV-H and HERV-W) are nonselectively copackaged. Assignment of cloned HML-2 gag and env cDNAs from Tera-1 retroviral particles to individual HML-2 loci in the human genome demonstrated that HML-2 RNA transcripts packaged into Tera-1 retroviral particles originate almost exclusively from an HML-2 provirus on chromosome 22q11.

Lack of immune responses against multiple sclerosis-associated retrovirus/human endogenous retrovirus W in patients with multiple sclerosis.

The multiple sclerosis-associated retrovirus (MSRV), originally identified in cell cultures from patients with multiple sclerosis (MS), is closely related to the human endogenous retrovirus family type W (HERV-W). Different lines of evidence appear compatible with a potential role of MSRV/HERV-W in the pathogenesis of MS. The authors therefore analyzed humoral and cellular immune responses against MSRV/HERV-W antigens in patients with MS, patients with other inflammatory and noninflammatory neurological diseases, and healthy controls, using indirect immunofluorescence and enzyme-linked immunospot assays.

Estimation of human herpesvirus 8 prevalence in high-risk patients by analysis of humoral and cellular immunity.

Background: Immunocompromized individuals, such as patients with end-stage renal disease, transplant recipients, and HIV-infected patients, are at increased risk of acquiring human herpesvirus (HHV)-8 associated infectious complications. The prevalence of HHV-8 infection generally is determined by detection of immunoglobulin G. However, because serological assays differ greatly, estimations on the actual HHV-8 prevalence vary considerably.

Physical and functional interactions of human endogenous retrovirus proteins Np9 and rec with the promyelocytic leukemia zinc finger protein.

Only few of the human endogenous retrovirus (HERV) sequences in the human genome can produce proteins. We have previously reported that (i) patients with germ cell tumors often make antibodies against proteins encoded by HERV-K elements, (ii) expression of the HERV-K rec gene in transgenic mice can interfere with germ cell development and induce carcinoma in situ, and (iii) HERV-K np9 transcript is overproduced in many tumors including breast cancers. Here we document that both Np9 and Rec physically and functionally interact with the promyelocytic leukemia zinc finger (PLZF) tumor suppressor, a transcriptional repressor and chromatin remodeler implicated in cancer and the self-renewal of spermatogonial stem cells.

Permanent loss of anti-HBc after reactivation of hepatitis B virus infection in an anti-HBs and anti-HBc-positive patient after allogeneic stem cell transplantation.

Background: Reactivation of a hepatitis B virus (HBV) infection after transplantation is associated with a high morbidity and mortality. HBV infections generally result in anti-HBc persisting lifelong.

Case Report: A 44-year-old female presented 10 years after allogeneic stem cell transplantation with a chronic hepatitis B.

Prevalence of herpes simplex virus (types 1 and 2), varicella-zoster virus, cytomegalovirus, and human herpesvirus 6 and 7 DNA in cerebrospinal fluid of Middle Eastern patients with encephalitis.

HSV-1 DNA was detected in 32 (30%) of 106 cerebrospinal fluid samples from patients with encephalitis. Cytomegalovirus, varicella-zoster virus, and human herpesvirus 6 (HHV-6) DNAs were each detected in three patients (3%); herpes simplex virus type 2 (HSV-2) and HHV-7 PCRs were negative. HSV detection was associated with seizure (P = 0.

Differences in CMV-specific T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation.

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation.

Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors.

Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs.

Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X.

We have recently identified Np9 as a novel nuclear protein produced by the human endogenous retrovirus K and were able to document the exclusive presence of np9 transcript in tumors and transformed cells. With the aim of studying whether Np9 has a role in tumorigenesis, a systematic search for interacting proteins was performed. Here, we identify the RING-type E3 ubiquitin ligase LNX (ligand of Numb protein X) as an Np9-interacting partner.

Evaluation of a new automated, standardized generic nucleic acid extraction method (total nucleic acid isolation kit) used in combination with cytomegalovirus DNA quantification by COBAS AMPLICOR CMV MONITOR.

The new generic Total Nucleic Acid Isolation kit improved the detection limit of a cytomegalovirus (CMV) PCR from 400 to 200 copies/ml. Sensitivity and specificity in 30 CMV-positive and 100 negative samples were 100%. Analytical performance was excellent.

HERV-K(HML-2) GAG/ENV antibodies as indicator for therapy effect in patients with germ cell tumors.

Germ cell tumors (GCT) are strictly associated with the expression of HERV-K(HML-2) proviruses, and the majority of GCT patients produce antibodies to structural proteins of these proviruses. The objective of our study was to determine the significance of the serological response to HERV-K(HML-2) Gag and Env proteins for diagnosis, management of GCT patients and estimation of the therapy success. The data document a strong association of HERV-K(HML-2) antibodies and the clinical manifestation of the disease and therapy success.

Is the cytomegalovirus serologic status always accurate? A comparative analysis of humoral and cellular immunity.

Background: The precise knowledge of cytomegalovirus (CMV) status is important in a variety of clinical settings such as transplantation or blood transfusion. There are, however, various situations where an immunoglobulin-based diagnostic approach has limitations.

Methods: The CMV status of 388 individuals was determined by the analysis of both CMV-specific immunoglobulins and cellular immunity using a standard enzyme-linked immunosorbent assay and a rapid-flow cytometric approach, respectively.

Risk of occupational human herpesvirus 8 infection for health care workers.

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is highly prevalent in certain risk groups (human immunodeficiency virus-infected patients, transplant recipients, and patients on hemodialysis). Heath care workers caring for these patients were found to be more frequently infected with HHV-8 than staff caring for other patients (P < 0.01).

Evaluation of four commercially available Epstein-Barr virus enzyme immunoassays with an immunofluorescence assay as the reference method.

Four commercially available enzyme immunoassays (EIAs) (Novitec, Biotest, Virotech, and DiaSorin) were evaluated, with an indirect immunofluorescence assay as the reference method, for Epstein-Barr virus (EBV) VCA (viral capsid antigen) immunoglobulin G (IgG), VCA IgM, or EBNA (EBV nuclear antigen) IgG at three different locations (Homburg, Stuttgart, and Dresden). Serum samples from 66 immunocompetent patients with infectious mononucleosis, 73 patients without prior EBV infection, and 96 patients with past EBV infections and 29 serum samples with possible cross-reactions to other herpesviruses were included. In addition, 25 samples from an extensively pretested panel that is commercially available (Boston Biomedica) were tested.

A novel gene from the human endogenous retrovirus K expressed in transformed cells.

Purpose: We investigated the expression of human endogenous retrovirus K (HERV-K) transcripts in various tumor tissues and transformed cell lines.

Experimental Design: We performed reverse transcription-PCR analysis to examine expression of env reading frame transcripts in mammary carcinoma biopsies, germ-cell tumor samples, ovarian carcinomas, and lymphocytes of leukemic patients, as well as in a variety of transformed cell lines. The novel np9 gene was analyzed by sequencing.

Evaluation of use of Epstein-Barr viral load in patients after allogeneic stem cell transplantation to diagnose and monitor posttransplant lymphoproliferative disease.

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disease (PTLD) continues to be a serious complication following transplantation. The aim of the present study was to evaluate the EBV load as a parameter for the prediction and monitoring of PTLD. The EBV load was analyzed by a quantitative competitive PCR with 417 whole-blood samples of 59 patients after allogeneic stem cell transplantation (SCT).