Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021345 (infectious mononucleosis)
 3,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subsequent to an infectious mononucleosis a 15 year old girl developed a thrombosis of the iliaca vein. Laboratory evaluation revealed a heterozygous form of protein C deficiency. An infusion with r-tPA (= recombinant tissue plasminogen activator) at a rate of 0.02 mg/kg BW/h over 96 hours failed to reopen the vessel. After intermittent heparin therapy longterm treatment with coumarin began. Three months later the iliaca vein was partially recanalised.
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PMID:[Pelvic vein thrombosis in protein C deficiency after infectious mononucleosis]. 811 74

Intranasal infection of mice with the murine gamma-herpesvirus MHV-68 results in an acute lytic infection in the lung, followed by the establishment of lifelong latency. Development of an infectious mononucleosis-like syndrome correlates with the establishment of latency and is characterized by splenomegaly and the appearance of activated CD8+ T cells in the peripheral blood. Interestingly, a large population of activated CD8+ T cells in the peripheral blood expresses the V beta 4+ element in their TCR. In this report we show that MHV-68 latency in the spleen after intranasal infection is harbored in three APC types: B cells, macrophages, and dendritic cells. Surprisingly, since latency has not previously been described in dendritic cells, these cells harbored the highest frequency of latent virus. Among B cells, latency was preferentially associated with activated B cells expressing the phenotype of germinal center B cells, thus formally linking the previously reported association of latency gene expression and germinal centers to germinal center B cells. Germinal center formation, however, was not required for the establishment of latency. Significantly, although three cell types were latently infected, the ability to stimulate V beta 4+CD8+ T cell hybridomas was limited to latently infected, activated B cells.
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PMID:Latent murine gamma-herpesvirus infection is established in activated B cells, dendritic cells, and macrophages. 1087 86

Signaling lymphocytic activation molecule (SLAM) is a CD2-related surface receptor expressed by activated T cells and B cells. SLAM is a self ligand and enhances T cellular proliferation and IFN-gamma production. A defective SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal mononucleosis based on the inability to control EBV. We report that SLAM augments TCR-mediated cytotoxicity. In normal CD4(+) and CD8(+) T cells, SLAM enhanced TCR-mediated cytotoxicity. In CD4(+) and CD8(+) Herpesvirus saimiri (H.saimiri) infected T cells, SLAM engagement alone triggered cytotoxicity. Using H.saimiri-transformed T cells as a model system we found that SLAM-engagement promotes the release of lytic granules and a CD95-independent killing that requires extracellular Ca(2+), cytoskeletal rearrangements, and signaling mediated by mitogen-activated protein kinase kinases MEK1/2. SLAM-enhanced cytotoxicity implies an immunoregulatory function by facilitating the elimination of APC and a role in overcoming infections with pathogens requiring a cytotoxic immune response.
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PMID:Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity. 1153 73

Splenic infarction is a common cause of left upper quadrant pain and must be suspected in patients with hematologic or thromboembolic conditions and signs of localized or systemic inflammation. Although several mechanisms have been proposed for splenic infarction in patients with various hematologic disorders, hereditary spherocytosis (HS) is usually not associated with an increased risk for thromboembolic events. We report a 13-year-old male with HS who was referred to our hospital with a 4-day history of fever and left upper quadrant pain. Ultrasound scans and magnetic resonance imaging showed lesions suggestive of splenic infarction. Initially, antibiotic treatment was started because secondary infection was suspected. However, 1 week after admission the patient developed typical clinical signs of acute infectious mononucleosis. Further laboratory work up confirmed the diagnosis of acute Epstein-Barr virus infection and additionally revealed protein C deficiency. This association has not been reported previously and may have contributed to the development of splenic infarction. Since infectious mononucleosis is a common cause for clinical consultations in adolescence, physicians caring for children with hematologic disorders should be particularly aware of those possible complications.
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PMID:Splenic infarction in a patient hereditary spherocytosis, protein C deficiency and acute infectious mononucleosis. 1860 54

Described herein is the case of a previously healthy 7-year-old girl who had splenic infarction. This lesion was identified 1 day after the first presentation of peri-umbilical and right upper quadrant pain. She had abnormal hepatic function and mild splenomegaly, and was diagnosed as having primary Epstein-Barr virus (EBV) infection. Coagulation profiles indicated low plasma activity of protein C (49%) and protein S (47%), which normalized 3 weeks later. Hypercoagulability in transient protein C and protein S deficiency might contribute to the development of splenic infarction in infectious mononucleosis.
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PMID:Splenic infarction in a child with primary Epstein-Barr virus infection. 2413 66

Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1). Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR), mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD002411 (http://proteomecentral.proteomexchange.org/dataset/PXD002411).
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PMID:Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling. 2671 15