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)

The role of neutrophils during Epstein-Barr virus (EBV) infection is not known. Disruption of the initial and nonspecific immune response may favor the spread of EBV infection. We have previously shown that EBV interacts with human neutrophils and modulates protein expression. In this study we have investigated the ability of EBV to infect neutrophils. Electron microscopy studies showed penetration of virus and its subsequent localization to the nucleus. The presence of viral genomes in isolated nuclei from neutrophils was also shown by polymerase chain reaction (PCR). Expression of viral transcripts like EBNA-2 (Epstein-Barr nuclear antigen-2) and ZEBRA (BamHI Z EBV replication activator) was not detected by reverse transcriptase (RT)-PCR, suggesting that EBV does not seem to establish a latent or a lytic infection in neutrophils. However, at 20 hours post-EBV infection, 77% of cells were apoptotic as compared to 22% in uninfected cell cultures, as evaluated by flow cytometry. This EBV-induced apoptosis was prevented by the addition of granulocyte-macrophage colony-stimulating factor to the cell cultures. Apoptotic cell death seems to implicate the Fas/Fas ligand (L) pathway, as reflected by an increase of Fas/Fas L expression on neutrophils treated with EBV and an increase of soluble Fas L, which may function in an autocrine/paracrine pathway to mediate cell death. Lastly, EBV genome was detected from neutrophils of infectious mononucleosis (IM) patients in contrast to neutrophils obtained from healthy EBV-seropositive donors. Our findings on the interactions of EBV with neutrophils will then provide new insights on the immunosuppressive effects associated with EBV infection.
 ...
PMID:Epstein-Barr virus infects and induces apoptosis in human neutrophils. 963 29

The Epstein-Barr virus (EBV) induces infectious mononucleosis (IM) and can be associated with chronic active EBV infection (CAEBV). Cytotoxic T lymphocytes (CTL) play an important role in excluding EBV-infected cells. Two cytotoxic mechanisms of CTL have been demonstrated: one perforin/granzyme-based and the other Fas (CD95)/Fas ligand (FasL)-based. To clarify these two pathways in CAEBV, we analyzed six patients with CAEBV and four patients with IM using immunohistochemical staining of the lymph nodes. In both CAEBV and IM, CD8+ T-cells increased in number, but CD56+ natural killer cells were rare. In four of six cases with CAEBV, approximately half the lymphocytes were positive for T cell-restricted intracellular antigens (TIA-1), which were recognized by the cytolytic granules of CTL. In IM, the number of TIA-1 positive cells was smaller than that in CAEBV. Fas-positive lymphocytes were frequently encountered in both CAEBV and IM. However, FasL-positive lymphocytes increased in three of six patients with CAEBV, but not in patients with IM. Except for one case with CAEBV, the number of perforin- and/or granzyme-positive cells was small in number in both CAEBV and IM cases. In double-staining FasL and EBV in situ hybridization, FasL-positive EBV-infected lymphocytes were detected in CAEBV but not in IM. In CAEBV, the Fas/FasL pathway and not perforin pathways appears to play an important role in the pathogenesis. The data suggest that EBV-infected lymphocytes may evade immune attack through the expression of FasL.
 ...
PMID:CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes: a possible mechanism of immune evasion in chronic active EBV infection. 1022 19

Epstein-Barr virus (EBV) acute infectious mononucleosis (AIM) is characterized by transient immunosuppression in vivo and increased T-cell apoptosis after ex vivo culture of AIM peripheral blood mononuclear cells. We undertook experiments to test whether EBV or purified virion envelope glycoprotein gp350 could contribute to Fas-mediated T-cell apoptosis. Our in vitro results indicate that EBV increased Fas expression in CD4(+) T cells and Fas ligand (FasL) expression in B cells and macrophages. Purified gp350 was also shown to significantly increase CD95 expression in CD4(+) T cells. When T-cell CD95 was cross-linked, EBV-stimulated T cells underwent apoptosis. The induction of T-cell CD95 by EBV followed by CD95 cross-linking with anti-CD95 monoclonal antibody resulted in a loss in the number of T cells responding to the T-cell mitogens, anti-CD3 antibody, and interleukin-2. These results indicate that, in addition to serving as a principal ligand for the attachment of virus to target cells, gp350 may also act as an immunomodulatory molecule that promotes T-cell apoptosis.
 ...
PMID:Epstein-Barr virus induces Fas (CD95) in T cells and Fas ligand in B cells leading to T-cell apoptosis. 1055 54

Although lymphocytosis and neutropenia are commonly associated with infectious mononucleosis (IM), the precise mechanisms involved remain unclear. Accumulated evidence has revealed that the apoptosis-mediating system, Fas receptor/Fas ligand (Fas-R/Fas-L), plays an important role in this disease. Recently, lymphocytes, monocytes, and neutrophils have been reported to constitutively express Fas-R, and the Epstein-Barr virus (EBV) has been shown to activate, in addition to B cells, peripheral blood CD8+ T cells, monocytes, and neutrophils. We elucidated cell surface expression and serum concentrations of Fas-R and Fas-L in patients with IM in an effort to more clearly define the role and contribution of apoptosis in this disease. The expression of lymphocyte surface Fas-L and Fas-R was significantly increased in patients with IM (P < .005 and P < .001, respectively), and among lymphocytes, CD4+ or CD8+ populations contained Fas-R+ as well as Fas-R- subpopulations. The constitutive Fas-R expression levels of monocytes and neutrophils were also increased in IM. Moreover, serum levels of both soluble Fas-L and Fas-R were significantly higher in patients with IM than in healthy volunteers (P < .001 and P < .0001, respectively). Positive relationships between the number of peripheral blood CD95+ lymphocytes and white blood cell count, number of lymphocytes, or number of CD4+ or CD8+ lymphocytes were observed. Our results suggest that the Fas-R/Fas-L system might play a role in eliminating EBV-infected or -activated peripheral blood cells by cell-to-cell contact or in an autocrine and/or paracrine fashion in patients with IM.
 ...
PMID:Cellular expressions and serum concentrations of Fas ligand and Fas receptor in patients with infectious mononucleosis. 1118 89

Epstein-Barr virus (EBV) associated diseases and studies performed in Japan are reviewed. Infectious mononucleosis is a common disease in Japanese infants. Chronic and severe EBV-infections include severe chronic active EBV-infection (SCAEBV), EBV-associated hemophagocytic syndrome, and mosquito allergy with granular lymphocyte proliferative disorder (GLPD). Autoimmune lymphoproliferative syndrome (ALPS), a disease caused by a defect in the Fas-Fas ligand pathway of cell-death, may develop into lymphoproliferative disease after early exposure to EBV. More than ten cases of X-linked lymphoproliferative syndrome (XLP) were discovered in Japanese children, and the frequency of post-transplant lymphoproliferative disorder (PTLD) increased after the number of patients receiving organ transplantation increased. Recently, an association of EBV with gastric carcinoma and hepatocellular carcinoma has been suggested. EBV-infected cells, such as B-cells, T-cells, NK-cells, and epithelial cells in EBV-associated diseases have also been clarified.
 ...
PMID:Overview of Epstein-Barr virus-associated diseases in Japan. 1246 60

Epstein-Barr virus (EBV) is known to be a causative agent of hemophagocytic lymphohistiocytosis (HLH). To investigate association of apoptosis in the pathogenesis of EBV-associated HLH, the serum EBV loads, and serum concentrations of soluble tumor necrosis factor receptor 1 (sTNF-R1), soluble Fas ligand, and cytochrome c were examined in 15 patients with EBV-associated HLH and 24 patients with infectious mononucleosis (IM). Levels of sTNF-R1 are known to reflect the biological activity of TNF-alpha and cytochrome c is a specific marker of apoptosis. EBV loads, and concentrations of sTNF-R1 and cytochrome c were significantly higher in patients with EBV-associated HLH than in patients with IM. On the other hand, there were no statistically significant differences in the concentrations of soluble Fas ligand. In patients with EBV-associated HLH, EBV loads, concentrations of sTNF-R1, and cytochrome c were correlated with each other. These results suggest that apoptosis, which is dependent on the EBV load and could be mediated by TNF-alpha, plays a major role in the pathophysiology of EBV-associated HLH.
 ...
PMID:Evaluation of apoptosis in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. 1641 9

The Epstein-Barr virus (EBV) infection is known to result in infectious mononucleosis, hemophagocytic syndrome, chronic active EBV infection, and lymphoma. Among them, hemophagocytic syndrome sometimes causes thrombocytopenia, which is often life threatening because of its hemorrhagic complications such as gastrointestinal bleeding and pulmonary alveolar hemorrhage. A young adult case of critical hemophagocytic syndrome after primary EBV infection is presented. Chemotherapy was performed using methyl prednisolone succinate, prednisolone, cyclosporin A, and 20 mg/kg of cyclophosphamide. The patient received intensive care, including plasma exchange for hepatic failure, extracorporeal membrane oxygenation for acute respiratory failure, and splenectomy for hemophagocytosis; however, the patient died of multiple organ failure, including fulminant hepatic failure. The pathologic examination of the resected specimen demonstrated infiltrated macrophages containing many phagocytosed erythrocytes. Further immunopathologic examination of these cells showed that the histiocyte markers were positive, whereas the T-cell marker was negative. In view of these findings, definite diagnosis of EBV-related hemophagocytic lymphohistiocytosis could not be made at that time. The immunohistologic examinations on the liver necropsy specimen provided the evidences suggesting the morbid activation of the hepatic stellate macrophage by EBV-infected T/NK cells and subsequent apoptosis induction of the liver cells through the Fas ligand pathway.
 ...
PMID:A case of hemophagocytic lymphohistiocytosis after the primary Epstein-Barr virus infection. 1763 96