Search results for "muro"
showing 10 items of 64 documents
The Putative Natural Killer Decoy Early Genem04(gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T…
2000
ABSTRACTSeveral early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, them152gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the “missing self.” The retention, however, is counteracted by them04early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 mi…
Processing and Presentation of Murine Cytomegalovirus pORFm164-Derived Peptide in Fibroblasts in the Face of All Viral Immunosubversive Early Gene Fu…
2002
ABSTRACTCD8 T cells are the principal effector cells in the resolution of acute murine cytomegalovirus (mCMV) infection in host organs. This undoubted antiviral and protective in vivo function of CD8 T cells appeared to be inconsistent with immunosubversive strategies of the virus effected by early (E)-phase genesm04,m06, andm152. The so-called immune evasion proteins gp34, gp48, and gp37/40, respectively, were found to interfere with peptide presentation at different steps in the major histocompatibility complex (MHC) class I pathway of antigen processing and presentation in fibroblasts. Accordingly, they were proposed to prevent recognition and lysis of infected fibroblasts by cytolytic T…
The Immune Evasion Paradox: Immunoevasins of Murine Cytomegalovirus Enhance Priming of CD8 T Cells by Preventing Negative Feedback Regulation▿
2008
ABSTRACTCytomegaloviruses express glycoproteins that interfere with antigen presentation to CD8 T cells. Although the molecular modes of action of these “immunoevasins” differ between cytomegalovirus species, the convergent biological outcome is an inhibition of the recognition of infected cells. In murine cytomegalovirus, m152/gp40 retains peptide-loaded major histocompatibility complex class I molecules in acis-Golgi compartment, m06/gp48 mediates their vesicular sorting for lysosomal degradation, and m04/gp34, although not an immunoevasin in its own right, appears to assist in the concerted action of all three molecules. Using the Ld-restricted IE1 epitope YPHFMPTNL in the BALB/c mouse m…
Cytomegalovirus Encodes a Positive Regulator of Antigen Presentation
2006
ABSTRACT Murine cytomegalovirus encodes three regulators of antigen presentation to antiviral CD8 T cells. According to current paradigms, all three regulators are committed to the inhibition of the presentation of antigenic peptides. Whereas m152/gp40 catalyzes the retention of peptide-loaded major histocompatibility complex (MHC) class I molecules in a cis -Golgi compartment, m06/gp48 binds stably to class I molecules and directs them into the cellular cargo-sorting pathway of lysosomal degradation. Regulator m04/gp34 also binds stably to class I molecules, but unlike m152 and m06, it does not downmodulate MHC class I cell surface expression. It has entered the literature as a direct inhi…
A novel transmembrane domain mediating retention of a highly motile herpesvirus glycoprotein in the endoplasmic reticulum
2010
Gene m164 of murine cytomegalovirus belongs to the large group of 'private' genes that show no homology to those of other cytomegalovirus species and are thought to represent 'host adaptation' genes involved in virus-host interaction. Previous interest in the m164 gene product was based on the presence of an immunodominant CD8 T-cell epitope presented at the surface of infected cells, despite interference by viral immune-evasion proteins. Here, we provide data to reveal that the m164 gene product shows unusual features in its cell biology. A novel strategy of mass-spectrometric analysis was employed to map the N terminus of the mature protein, 107 aa downstream of the start site of the pred…
Tumor Control in a Model of Bone Marrow Transplantation and Acute Liver-Infiltrating B-Cell Lymphoma: an Unpredicted Novel Function of Cytomegalovirus
2002
ABSTRACTTumor relapse and cytomegalovirus (CMV) infection are major concerns in the therapy of hematopoietic malignancies by bone marrow transplantation (BMT). Little attention so far has been given to a possible pathogenetic interplay between CMV and lymphomas. CMV inhibits stem cell engraftment and hematopoietic reconstitution. Thus, by causing maintenance of bone marrow aplasia and immunodeficiency, CMV could promote tumor relapse. Alternatively, CMV could aid tumor remission. One might think of cytopathogenic infection of tumor cells, induction of apoptosis or inhibitory cytokines, interference with tumor cell extravasation or tumor vascularization, or bystander stimulation of an antitu…
Identification of a Kd-restricted antigenic peptide encoded by murine cytomegalovirus early gene M84
2000
The two sister cytomegaloviruses (CMVs), human and murine CMV, have both evolved immune evasion functions that interfere with the major histocompatibility complex class I (MHC-I) pathway of antigen processing and presentation and are effectual in the early (E) phase of virus gene expression. However, studies on murine CMV have shown that E-phase immune evasion is leaky. An E-phase protein involved in immune evasion, namely m04-gp34, was found to simultaneously account for an antigenic peptide presented by the MHC-I molecule Dd. Recent work has demonstrated the induction of protective immunity specific for the E-phase protein M84-p65, one of two murine CMV homologues of the human CMV matrix …
Virally Infected Mouse Liver Endothelial Cells Trigger CD8+ T-Cell Immunity
2009
Background & Aims Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8 + T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8 + T-cell activation upon such stimulation. Methods Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo…
Early gene m18, a novel player in the immune response to murine cytomegalovirus
2002
The identification of all antigenic peptides encoded by a pathogen, its T cell ‘immunome’, is a research aim for rational vaccine design. Screening of proteome-spanning peptide libraries or computational prediction is used to identify antigenic peptides recognized by CD8 T cells. Based on their high coding capacity, cytomegaloviruses (CMVs) could specify numerous antigenic peptides. Yet, current evidence indicates that the memory CD8 T cell response in a given haplotype is actually focused on a few viral proteins. CMVs actively interfere with antigen processing and presentation by the expression of immune evasion proteins. In the case of murine CMV (mCMV), these proteins are effectual in th…
Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus
2002
Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven pos…