Search results for "Cytomegalovirus infection"

An antigen fragment encompassing the AD2 domains of glycoprotein B from two different strains is sufficient for differentiation of primary vs. recurr…

2001

Primary human cytomegalovirus (HCMV) infection during pregnancy is a frequent cause of fatal damage in populations with low prevalence of HCMV. Differentiation of primary vs. recurrent HCMV infection is an important issue in prenatal counseling. Antibodies specific for viral glycoproteins become detectable only with considerable delay with relation to HCMV infection or IgG seroconversion. Thus, lack of glycoprotein specific (gp-specific) antibodies can serve as a convenient indicator to identify those pregnant women that bear an elevated risk for HCMV transplacental transmission and fetal sequelae. In the opposite case, presence of gp-specific antibodies virtually excludes HCMV primary infe…

Suppression of CD8+ T cell recognition in the immediate-early phase of human cytomegalovirus infection.

2012

Human cytomegalovirus (HCMV) interferes with MHC class I-restricted antigen presentation and thereby reduces recognition by CD8+ T-cells. This interference is mediated primarily by endoplasmic reticulum-resident glycoproteins that are encoded in the US2–11 region of the viral genome. Such a suppression of recognition would be of particular importance immediately after infection, because several immunodominant viral antigens are already present in the cell in this phase. However, which of the evasion proteins gpUS2–11 interfere(s) with antigen presentation to CD8+ T-cells at this time of infection is not known. Here we address this question, using recombinant viruses (RV) that express only o…

Longitudinal analysis of human cytomegalovirus glycoprotein B (gB)-specific and neutralizing antibodies in AIDS patients either with or without cytom…

2001

Serum neutralizing and glycoprotein B (gB)-specific antibody levels were monitored prospectively in AIDS patients who either did or did not develop human cytomegalovirus (HCMV) end-organ disease, to delineate further the role of antibodies in protecting against HCMV disease. Antibody levels declined substantially (at least 4-fold) only in patients who developed HCMV disease; this decline in turn occurred concurrently with antigenemia. Nevertheless, AIDS patients who remained free of HCMV disease and did not become antigenemic during the follow-up period maintained stable levels of serum antibodies, with only minor fluctuations. The impact of HAART on the levels of functional anti-HCMV antib…

Enzyme Affinity Assays Involving a Single-Use Electrochemical Sensor. Applications to the Enzyme Immunoassay of Human Chorionic Gonadotropin Hormone …

2000

Identification of a Conserved HLA-A2-Restricted Decapeptide from the IE1 Protein (pUL123) of Human Cytomegalovirus

2002

Abstract Control of human cytomegalovirus (HCMV) infection is predominantly mediated by cytolytic CD8 + T lymphocytes (CTL). Among the roughly 200 HCMV-encoded polypeptides, the tegument protein pp65 (ppUL83) and the nonstructural IE1 protein are considered to be dominant CTL targets. Yet the importance of CTL against IE1 for protective immunity against HCMV reactivation and disease has remained elusive. Analyses have been difficult, as all MHC class I presented peptides of IE1 defined so far are located in parts of the protein that are variable between viral strains. In this study a conserved decameric peptide from IE1 (P6, IE1 354–363 ) that bound to HLA-A2 was identified. Using peptide-p…

Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread

2015

Herpesviruses form different gH/gL virion envelope glycoprotein complexes that serve as entry complexes for mediating viral cell-type tropism in vitro; their roles in vivo, however, remained speculative and can be addressed experimentally only in animal models. For murine cytomegalovirus two alternative gH/gL complexes, gH/gL/gO and gH/gL/MCK-2, have been identified. A limitation of studies on viral tropism in vivo has been the difficulty in distinguishing between infection initiation by viral entry into first-hit target cells and subsequent cell-to-cell spread within tissues. As a new strategy to dissect these two events, we used a gO-transcomplemented ΔgO mutant for providing the gH/gL/gO…

Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice

2015

Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the conte…

Clinically-based determination of safe DNAemia cutoff levels for preemptive therapy or human cytomegalovirus infections in solid organ and hematopoie…

2004

Transplantation Centers using human cytomegalovirus (HCMV) antigenemia-based preemptive therapy will need to replace in the near future the antigenemia assay with a more standardized and automatable assay, such as a molecular assay quantifying HCMV DNA in blood (DNAemia). Thus, in view of replacing antigenemia with clinically safe cutoff values, DNAemia levels corresponding to antigenemia cutoffs guiding HCMV preemptive therapy were determined retrospectively in solid organ and hematopoietic stem cell transplant recipients (HSCTR) using an "in-house" quantitative PCR (QPCR) method. Since preemptive therapy had prevented appearance of HCMV disease in all patients tested, DNA cutoffs determin…

Immune evasion proteins gpUS2 and gpUS11 of human cytomegalovirus incompletely protect infected cells from CD8 T cell recognition

2009

AbstractHuman cytomegalovirus (HCMV) encodes four glycoproteins, termed gpUS2, gpUS3, gpUS6 and gpUS11 that interfere with MHC class I biosynthesis and antigen presentation. Despite gpUS2–11 expression, however, HCMV infection is efficiently controlled by cytolytic CD8 T lymphocytes (CTL). To address the role of gpUS2 and gpUS11 in antigen presentation during viral infection, HCMV mutants were generated that expressed either gpUS2 or gpUS11 alone without coexpression of the three other proteins. Fibroblasts infected with these viruses showed reduced HLA-A2 and HLA-B7 surface expression. Surprisingly, however, CTL directed against the tegument protein pp65 and the regulatory IE1 protein stil…

Stalemating a clever opportunist: lessons from murine cytomegalovirus.

2003

Abstract Cytomegaloviruses and their specific hosts have come to an arrangement that avoids disease but allows the viruses to persist in the individual host and to spread in the host species. Recent work has uncovered some of the molecular details of this evolutionary “contract for mutual survival.” Cytomegaloviruses encode proteins, referred to as “immunoevasins,” which are specifically committed to subvert the immune defense of the host for evading virus elimination. In reply, the hosts have evolved countermeasures to overcome the viral immunoevasins and present antigenic peptides to an extent that is sufficient for confining virus replication to below a harmful level. Accordingly, cytome…