Search results for "human cytomegalovirus"
showing 10 items of 92 documents
Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.
2016
Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGI…
ID: 37
2015
During the early phase of human cytomegalovirus (HCMV) infection, the Interferon- γ -Inducible factor 16 (IFI16) behaves as a pattern recognition receptor (PRR) sensing viral DNA and triggering antiviral cytokine release. Later on, it restricts virus replication by down-regulating expression of viral genes committed to DNA synthesis including UL54 and UL44. These activities are modulated by viral proteins including pUL83, a tegument protein involved in viral evasion. Here, we demonstrate that pUL83 interacts with IFI16 relieving its inhibitory activity on UL54 gene transcription. We also establish that, starting from 48 h post-infection, IFI16 is stabilized and protected from degradation by…
Assessment of human cytomegalovirus specific T cell immunity in human immunodeficiency virus infected patients in different disease stages following …
2004
T cell immunity to human cytomegalovirus (HCMV) was assessed in HAART-treated HIV-1 infected patients (9 asymptomatic, CDC group A; and 22 symptomatic, CDC group B), and in eight HIV-1 long term non-progressors. Patients were either prospectively or cross-sectionally examined for CD4(+) T cell counts, HIV RNA load, HCMV leukoDNAemia, HCMV DNA in urine, lymphoproliferative response (LPR) to HCMV and phytohemagglutinin (PHA), and cytokine secretion (IFN-gamma and IL-4) by HCMV-stimulated peripheral blood mononuclear cell (PBMC) cultures. No patient either progressed to clinical AIDS or developed HCMV active infection during the study period. Twenty-nine patients responded to HAART, though 12 …
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…
Tetraspanin CD151 Promotes Initial Events in Human Cytomegalovirus Infection.
2016
ABSTRACT Human cytomegalovirus (HCMV), a betaherpesvirus, can cause life-threatening disease in immunocompromised individuals. Viral envelope glycoproteins that mediate binding to and penetration into target cells have been identified previously. In contrast, cellular proteins supporting HCMV during entry are largely unknown. In order to systematically identify host genes affecting initial steps of HCMV infection, a targeted RNA interference screen of 96 cellular genes was performed in endothelial cells by use of a virus strain expressing the full set of known glycoprotein H and L (gH/gL) complexes. The approach yielded five proviral host factors from different protein families and eight an…
γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia.
2013
Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV reactivation after allo-SCT and reduced leukemic relapse. Given the potential of Vδ2-negative γδT cells to recognize CMV-infected cells and tumor cells, the molecular biology of distinct γδT-cell subsets expanding during CMV reactivation after allo-SCT was investigated. Vδ2(neg) γδT-cell expansions after CMV reactivation were observed not only with conventional but also cordblood donors. Expanded γδT cells were ca…
Polo-like kinase 1 as a target for human cytomegalovirus pp65 lower matrix protein
1999
ABSTRACT Human cytomegalovirus (HCMV) pp65 protein is the major constituent of viral dense bodies but is dispensable for viral growth in vitro. pp65 copurifies with a S/T kinase activity and has been implicated in phosphorylation of HCMV IE1 immediate-early protein and its escape from major histocompatibility complex 1 presentation. Furthermore, the presence of pp65 correlates with a virion-associated kinase activity. To clarify the role of pp65, yeast two-hybrid system (THS) screening was performed to identify pp65 cellular partners. A total of 18 out of 48 yeast clones harboring cDNAs for putative pp65 binding proteins encoded the Polo-like kinase 1 (Plk1) C-terminal domain. Plk1 behaved …
The Abundant Tegument Protein pUL25 of Human Cytomegalovirus Prevents Proteasomal Degradation of pUL26 and Supports Its Suppression of ISGylation
2018
The tegument of human cytomegalovirus (HCMV) virions contains proteins that interfere with both the intrinsic and the innate immunity. One protein with a thus far unknown function is pUL25. The deletion of pUL25 in a viral mutant (Towne-ΔUL25) had no impact on the release of virions and subviral dense bodies or on virion morphogenesis. Proteomic analyses showed few alterations in the overall protein composition of extracellular particles. A surprising result, however, was the almost complete absence of pUL26 in virions and dense bodies of Towne-ΔUL25 and a reduction of the large isoform pUL26-p27 in mutant virus-infected cells. pUL26 had been shown to inhibit protein conjugation with the in…
Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.
2005
Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3zeta from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction w…
Are Morphological or Functional Changes in the Carotid Artery Wall Associated With Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Her…
2000
Background and Purpose —Chronic infection with Chlamydia pneumoniae , Helicobacter pylori , cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall. Methods —In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a intern…