Killer Cell Defect and Lack or Loss of Antibodies to Epstein-Barr Virus Glycoproteins in Chronic Active EBV

The significant function of cytokines includes maintenance of cell survival as well as induction of cell differentiation and/or proliferation. We demonstrate here that interferon-γ (IFN-γ) plays a role for progression of Epstein-Barr virus (EBV)-infected natural killer cell leukemia (NK leukemia) through maintaining cell survival. NK leukemia cells obtained from 7 patients had clonal episomal forms of EBV, indicating that the leukemic cells were of clonal origin. Although normal NK cells constitutively expressed Bcl-2, the EBV-infected NK leukemia cells lacked endogenous Bcl-2 expression and were hypersensitive to apoptosis in vitro. The addition of IFN-γ to the culture significantly inhibited their spontaneous apoptosis without inducing cell proliferation or upregulation of Bcl-2. The NK leukemia cells constitutively secreted IFN-γ, and the patients’ sera contained a high concentration of IFN-γ, levels that were high enough to prevent NK leukemia cells from apoptosis. Bcl-XL was not involved in the IFN-γ–induced NK leukemia cell survival. These data suggest that the acquisition of IFN-γ–mediated autocrine survival signals, other than Bcl-2 or BCL-XL, might be important for the development of EBV-infected NK leukemia.

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Anti‐tumor effects of suberoylanilide hydroxamic acid on Epstein–Barr virus‐associated T cell and natural killer cell lymphoma

Cancer Science ◽

10.1111/cas.12418 ◽

2014 ◽

Vol 105 (6) ◽

pp. 713-722 ◽

Cited By ~ 10

Author(s):

Mohammed N.A. Siddiquey ◽

Hikaru Nakagawa ◽

Seiko Iwata ◽

Tetsuhiro Kanazawa ◽

Michio Suzuki ◽

...

Keyword(s):

T Cell ◽

Natural Killer Cell ◽

Natural Killer ◽

Hydroxamic Acid ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

Killer Cell ◽

Suberoylanilide Hydroxamic Acid ◽

Barr Virus ◽

Epstein Barr

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Epstein–Barr Virus Primary Infection Complicated by Hemophagocytic Lymphohistiocytosis and Plasmablastic Lymphoma in a HIV-Negative Patient

Case Reports in Hematology ◽

10.1155/2019/7962485 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Nan Chen ◽

Mike Perez ◽

Martha Mims

Keyword(s):

Bone Marrow ◽

Hemophagocytic Lymphohistiocytosis ◽

Epstein Barr Virus ◽

Killer Cell ◽

High Volume ◽

Immune Dysregulation ◽

Gastric Biopsy ◽

Plasmablastic Lymphoma ◽

Barr Virus ◽

Epstein Barr

EBV (Epstein–Barr virus) viremia causes immune dysregulation through various mechanisms, and we are understanding more that mutations in B, T, and NK (natural killer) cell signaling pathways allow EBV complications such as HLH (hemophagocytic lymphohistiocytosis) and lymphomas to arise. Here, we report a 20-year-old previously healthy, HIV- (human immunodeficiency virus-) negative male who presented with fevers, sore throat, and lymphadenopathy (LAD). He was found to have EBV viremia, pancytopenia, and elevated LFTs (liver function tests) suspicious for HLH. Bone marrow biopsy and elevated IL-2 (interleukin) receptor confirmed this diagnosis. Additionally, gastric biopsy confirmed diagnosis of plasmablastic lymphoma (PBL), a rare, aggressive HIV- and EBV-associated lymphoma. Both bone marrow and gastric biopsy showed evidence of EBV. Patients with EBV complications should have a rigorous workup to characterize the full extent of immune dysregulation including genetic testing at a high-volume center.

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