Epstein–Barr virus latent genes

Kang, Myung Soo; Kieff, Elliott

doi:10.1038/emm.2014.84

Cited by 295 publications

(272 citation statements)

References 321 publications

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“…First, based upon frequency, EBV infection may contribute to MM pathogenesis in subsets of patients (36). The main antigenic target, EBNA-1, is expressed in 3 types of latency observed in EBV-associated B cell malignancies; it is essential for EBV persistence and transcription (37)(38)(39). Existing drugs target the main signaling molecules or pathways altered by EBNA-1, notably p53/TP53, ubiquitin-and proteasome-dependent proteolysis, and the NF-κB pathway (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Bosseboeuf¹,

Feron²,

Tallet³

et al. 2017

JCI Insight

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International audienceSubsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients

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Section: Discussionmentioning

confidence: 99%

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Bosseboeuf¹,

Feron²,

Tallet³

et al. 2017

JCI Insight

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“…EBNA1 is the only viral protein consistently expressed during all forms of latency and in all EBV-associated malignancies (9,10). It is potentially a universal target for immune recognition of EBV-infected normal or malignant cells (10).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear antigen-1 (NA1) protein is expressed during latent and lytic cycles, binding to a replication origin within the viral genome. It also mediates replication and partitioning of the episome during the division of the host cell, and is essential for the maintenance of the viral genome in latency (8)(9)(10)(11). Since NA1 protein is expressed in EBV-infected cells, including cancer cells or cells in the cancer microenvironment, it may act as an antigen to induce immune responses if the microenvironment is suitable for the induction of humoral responses directed at NA1 (7).…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma

Jiang

et al. 2017

Oncology Letters

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Abstract. Nuclear antigen-1 (NA1) protein of Epstein-Barr virus (EBV) is expressed in EBV-infected cells in the microenvironment of cancer. Since immune cells infiltrate abundantly in nasopharyngeal carcinoma (NPC) tumor tissues, we hypothesized that the local tumor microenvironment may perform an important role in the production of antibodies directed at NA1. Furthermore, we hypothesized that anti-NA1 antibody originating in the local microenvironment could be secreted into the saliva of patients with NPC. In the present study, 20 healthy controls and 39 patients with NPC treated with intensity-modulated radiation therapy were recruited for the study. Saliva and serum samples were collected from the NPC patients, and nasopharyngeal tissue samples from the patients with NPC. The titers of anti-NA1 antibody [immunoglobulin A (IgA)] were determined by ELISA. Expression of NA1, human leukocyte antigen-antigen D related (HLA-DR), cluster of differentiation (CD)80, CD86, CD3, CD4, CD19 and IgA was detected by immunohistochemical staining on paraffin-embedded nasopharyngeal tissue sections. Anti-NA1 antibodies were detected in the serum and saliva samples of the patients with NPC. In infiltrating cells, expression of HLA-DR, CD80, CD86, CD3, CD4, CD19 and IgA was detected, indicating that dendritic cells, T lymphocytes and B lymphocytes were all present in the local tumor tissues. Furthermore, expression of EBNA1 protein was detected on the membrane of the NPC tumor cells. Therefore, the NPC tumor microenvironment has the potential to initiate a humoral response to EBNA1 by producing IgA antibodies.

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“…Correlations with patients' age were not found, whereas cigarette smoking is a recognized risk factor. [46,47]. In their own research, 62.5% of the total were male, and over 40% were more than 60 years old.…”

Section: Cancers Associated With Ebv Infection Include [2 8 14 23-mentioning

confidence: 99%

Epstein-Barr Virus – pathogenesis, latency and cancers

Kliszczewska¹,

Jarzynski²,

Boguszewska³

et al. 2017

J Pre Clin Clin Res.

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The Epstein-Barr virus (EBV) was discovered in 1964 by Michael Anthony Epstein and Yvonne Barr, who discovered a herpesvirus-like infectious agent in a biopsy specimen from a patient with Burkitt's lymphoma. This virus belongs to the Herpesviridae family (subfamily Gammaherpesvirinae, genus Lymphocryptovirus). EBV is a ubiquitous herpesvirus that is causally associated with various malignant tumours. According to the current nomenclature, it was named human herpesvirus type 4 (human herpesvirus 4 -HHV-4). Primary infection usually occurs in childhood. In developing countries, the infection rate among young children is higher than in developed countries. It was the first human tumour virus and it is currently categorized as a group-1 carcinogen due to its association with various cancers. It is estimated that over 90% of the adult population has been infected with this pathogen, but only a minority will develop the disease. EBV establishes latent infection characterized by the expression of a limited number of viral genes called latent genes. Moreover, during its life cycle, EBV periodically reactivates and can be transmitted to other susceptible hosts. The oral cavity is the main site of EBV occurrence and the most common source of infection. This study discusses EBV frequency and its association with the occurrence of malignant tumours and the pathways of tumour progression.

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Epstein–Barr virus latent genes

Cited by 295 publications

References 321 publications

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma

Epstein-Barr Virus – pathogenesis, latency and cancers

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