A 20-month-old male infant with multiorgan dysfunction after Epstein-Barr virus (EBV) infection developed Reye's syndrome. He also suffered from acute liver failure, life-threatening cerebral edema, severe disseminated intravascular coagulation (DIC), and myocardial involvement. EBV infection aggravated the progress of Reye's syndrome, leading to death despite full supportive and symptomatic therapy. This critical case suggested that pediatricians should pay attention to multiorgan involvement of severe EBV infection.
Epstein-Barr Virus Infections/complications* ; Fatal Outcome ; Herpesvirus 4, Human/physiology* ; Humans ; Infant ; Male ; Multiple Organ Failure/complications* ; Reye Syndrome/virology*

OBJECTIVETo analyze the prevalence of Epstein Barr Virus (EBV) infection in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe occurrence of EBV viremia, EBV disease and post-transplant lymphoproliferative disease (PTLD) were retrospectively analyzed in 736 patients received allo-HSCT in single-center from 1st January 2012 through July 31th, 2014.

RESULTSOf 736 patients (302 male and 434 females) with a median age of 31 (2 to 62) years old, EBV infection occurred in 181 patients, the total incidence of EBV infection was 27.6%, with a median time of 57 (16 to 829) days. The cumulative incidences of probable EBV disease and PTLD were 7.2% (13/181) and 2.8% (5/181). Viral load higher than 1.0×10(4) copies/ml occurs in 130 patients, of which 67 patients received rituximab as pre-empty prophylaxis and significantly reduced the incidences of probable EBV disease and PTLD (6.0% vs 22.2%, P=0.009). The mortality was 27.6% in all patients with EBV infection: 24.5% in EBV viremia, 53.8% in probable EBV disease, and 60.6% in PTLD. By univariate and multivariate analysis, the use of anti-thymocyte globulin (ATG), HLA-mismatch HSCT, cGVHD and CMV reactivation were independent risk factors for EBV infection. The time of first EBV reactivation was closely related with cGVHD(OR=0.620, 95%CI 0.453-0.849, P=0.003) and bone marrow or cord blood (OR=1.156, 95%CI 1.022-2.250, P=0.039) as source of stem cells for transplantation.

CONCLUSIONEBV reactivation is a common complication in patients with allo-HSCT, especially high mortality in PTLD and probable EBV disease. The use of ATG, HLA-mismatch HSCT, cGVHD and CMV reactivation were independent risk factors for EBV infection. The usage of rituximab as pre-empty prophylaxis may reduce the incidences of probable EBV disease and PTLD.

Adolescent ; Adult ; Antilymphocyte Serum ; therapeutic use ; Child ; Child, Preschool ; Epstein-Barr Virus Infections ; complications ; Female ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human ; Humans ; Incidence ; Lymphoproliferative Disorders ; complications ; virology ; Male ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Rituximab ; therapeutic use ; Transplantation, Homologous ; Viral Load ; Virus Activation ; Young Adult

Africa ; epidemiology ; Asia, Southeastern ; epidemiology ; Carcinoma ; Epstein-Barr Virus Infections ; complications ; epidemiology ; virology ; Herpesvirus 4, Human ; pathogenicity ; Humans ; Middle East ; epidemiology ; Nasopharyngeal Neoplasms ; epidemiology ; etiology ; virology

Extranodal NK/T cell lymphoma is a relatively uncommon type of non-Hodgkin's lymphoma, which is prevalently distributed in Asia and South America, and is highly associated with Epstein-Barr virus (EBV) infection. Due to its highly aggressive course and poor response to treatment because of its multi-drug resistance, for the timebeing there is not yet a definite treatment strategy. The clinical manifestation, pathological diagnosis and the progress of treatment methods of ENTNKCL are reviewed below.
Epstein-Barr Virus Infections ; complications ; Herpesvirus 4, Human ; Humans ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; therapy ; virology

Castleman Disease ; virology ; Epstein-Barr Virus Infections ; complications ; Herpesvirus 4, Human ; Humans

Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.
Cell Transformation, Viral ; Epstein-Barr Virus Infections/*complications ; Herpesvirus 4, Human/*physiology ; Humans ; Killer Cells, Natural/immunology/metabolism/*pathology/*virology ; Lymphoproliferative Disorders/diagnosis/*etiology/therapy ; T-Lymphocytes/immunology/metabolism/*pathology/*virology

The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein-Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described.
Animals ; Disease Models, Animal ; Epstein-Barr Virus Infections/complications/immunology/*virology ; Herpesvirus 4, Human/*physiology ; Heterografts ; Humans ; Killer Cells, Natural/pathology/virology ; Lymphoproliferative Disorders/etiology ; Mice ; Mice, SCID ; T-Lymphocytes/pathology/virology

OBJECTIVETo study the clinicopathologic features of Hodgkin lymphoma (HL) occurring in northern China, association with Epstein-Barr virus (EBV) infection and concordance between EBV protein immunohistochemistry (IHC) and in-situ hybridization (ISH).

METHODSTwo hundred and thirty-five cases were collected and their HE and IHC slides were reviewed to confirm the diagnosis and sort of HLs. All cases were performed with IHC staining for LMP-1 protein and ISH of EBV-encoded RNAs (EBER) was done in 101 cases to detect the existence of EBV.

RESULTSThe incidence peak was between age 25 and 35 years, followed by another peak between age 56 to 60 years. There were 135 males and 100 females. The tumor involved lymph nodes in 217 cases, and extranodal sites in 18 cases. There were 3 cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and 232 cases of classical Hodgkin lymphoma. All tumors were stained for CD30, CD20, CD3. CD30 was expressed in 227 cases (96.6%), CD20 was expressed in 53 cases (22.5%) with different level of intensity. CD3 was expressed only in 1 case (0.4%). CD15 staining was performed in 224 cases and 117 (52.2%) cases were positive. PAX-5 were performed in 213 cases and 160 (75.1%) cases showed weak to moderate expressions. Two hundred and thirty-five cases were immunohistochemically stained with LMP1 and 72 (30.6%) cases were positive. Meanwhile, EBER ISH were applied in 101 cases, and 40 cases (39.6%) were found positive. LMP1 was expressed in 30 cases among those EBER-positive cases, while LMP1 was only detected in 5 cases of the EBER-negative cases. There was no statistically significantce between LMP1 IHC and EBER ISH by pared chi-square test (P = 0.3), the overall concordance rate was 85.2%.

CONCLUSIONSThere was a bimodal age distribution in our group of HL cases from the northern part of China, with slight male predominance and mainly nodal involvement. Nodular sclerosis (NS) and mixed cellularity (MC) were major histologic subtypes. When it was compared with the EBER ISH method in detection EBV infection of HL, the more economical and convenient LMP1 IHC showed both high degree of consistency and overall concordance rate.

Adult ; Age Distribution ; Antigens, CD ; analysis ; China ; epidemiology ; Epstein-Barr Virus Infections ; complications ; epidemiology ; Female ; Herpesvirus 4, Human ; genetics ; isolation & purification ; Hodgkin Disease ; immunology ; pathology ; virology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Incidence ; Male ; Middle Aged ; RNA, Viral ; analysis ; Sex Distribution

Latent Epstein-Barr virus (EBV) infection has a substantial role in causing many human disorders. The persistence of these viral genomes in all malignant cells, yet with the expression of limited latent genes, is consistent with the notion that EBV latent genes are important for malignant cell growth. While the EBV-encoded nuclear antigen-1 (EBNA-1) and latent membrane protein-2A (LMP-2A) are critical, the EBNA-leader proteins, EBNA-2, EBNA-3A, EBNA-3C and LMP-1, are individually essential for in vitro transformation of primary B cells to lymphoblastoid cell lines. EBV-encoded RNAs and EBNA-3Bs are dispensable. In this review, the roles of EBV latent genes are summarized.
Epstein-Barr Virus Infections/complications/virology ; Epstein-Barr Virus Nuclear Antigens/genetics/metabolism ; *Genes, Viral ; Herpesvirus 4, Human/*physiology ; Humans ; MicroRNAs/genetics ; Neoplasms/etiology ; Protein Binding ; RNA, Viral/genetics ; Viral Matrix Proteins/genetics/metabolism ; *Virus Latency

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders.
B-Lymphocytes/*pathology/*virology ; Diagnosis, Differential ; Disease Management ; Epstein-Barr Virus Infections/*complications ; Herpesvirus 4, Human/*physiology ; Humans ; Lymphoproliferative Disorders/*diagnosis/*etiology/therapy