scholarly journals Recombinant Human Interferon-Gamma: Prospects for the Treatment of Chronic Epstein-Barr Viral Infection

2022 ◽  
Author(s):  
Irina A. Rakityanskaya ◽  
Tatiana S. Ryabova
Keyword(s):  
Interferon Gamma ◽  
Lymphocyte Culture ◽  
Human Interferon ◽  
Treatment Regimens ◽  
Barr Virus ◽  
Long Time ◽  
Group 3 ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Group 2

Infection of Epstein-Barr virus (EBV) is about 90% among people over the age of 40. The EBV causes a chronic infection that is characterized by chronic or recurrent symptoms and persists for a long time. Recombinant interferon-gamma (IFN-γ) has high clinical and antiviral efficacy in the treatment of herpesvirus infections. 110 patients with chronic EBV infection were examined. The patients were divided into three groups for different treatment regimens: Group 1—IFN-γ therapy (15 injections of Ingaron i/m, 500,000 IU every other day); Group 2—valaciclovir (Valtrex 500 mg × 2 times/day, orally for 2 months); Group 3—valganciclovir (Valcyte 450 mg × 2 times/day, orally for 2 months) and IFN-γ (10–20 injections of Ingaron i/m, 500,000 IU every other day). The best results were obtained in group 3–73.07% negative PCR. In this group, the combination of valganciclovir + IFN-γ was different. We showed that the efficacy of therapy in patients with chronic EBV is determined by the duration of INF-γ administration. We also determined spontaneous and induced production of IFN-α and -γ cytokines in serum and in lymphocyte culture. We demonstrated that in patients with an initially low level of induced IFN-γ, the production of this cytokine significantly increased in three months after the end of therapy.

scholarly journals How immunologic and genetic biomarkers impact Hodgkin lymphoma classification, diagnosis, and management: a huge potential that yet needs to be exploited

2017 ◽  
Vol 33 (2) ◽  
pp. 137-140 ◽  
Author(s):  
Antonino Carbone ◽  
Annunziata Gloghini
Keyword(s):  
Hodgkin Lymphoma ◽  
Molecular Genetic ◽  
Scientific Basis ◽  
Grey Zone ◽  
Molecular Virology ◽  
Barr Virus ◽  
Long Time ◽  
Modern Classification ◽  
Epstein Barr

“Ne è passata di acqua sotto i ponti.” It has been a long time since the diagnosis of Hodgkin lymphoma (HL) was exclusively based on the detection of typical Reed-Sternberg cells and the recognition of the characteristic morpho-histological background, as well as on the pathologist’s skill. The discovery of immunologic, molecular genetic and virologic biomarkers has provided an objective contribution to the diagnosis and a scientific basis for a modern classification of HL. Recent updates have clarified the nature of the so-called nodular lymphocyte predominant HL and its link to the T-cell/histiocyte-rich large B-cell lymphomas as well as its relationship with the lymphocyte-rich subset of classical HL (CHL). Molecular virology studies assessed a role for the Epstein-Barr virus in the pathogenesis of a fraction of CHL of the general population, and virtually in all cases of CHL occurring in people infected by HIV. Finally, immunologic and genetic findings corroborated the existence of grey zone lymphomas at the edges of CHL. Overall, these advances provided additional and useful information to address the treatment of patients affected by HL.

Interferon-γ Prevents Apoptosis in Epstein-Barr Virus-Infected Natural Killer Cell Leukemia in an Autocrine Fashion

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3494-3504 ◽  
Author(s):  
Shin-ichi Mizuno ◽  
Koichi Akashi ◽  
Koichi Ohshima ◽  
Hiromi Iwasaki ◽  
Toshihiro Miyamoto ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Cell Survival ◽  
Epstein Barr Virus ◽  
Killer Cell ◽  
Interferon Γ ◽  
Leukemia Cells ◽  
Cell Leukemia ◽  
Barr Virus ◽  
Ifn Γ ◽  
Epstein Barr

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.

scholarly journals Tonsillar CD56brightNKG2A+ NK cells restrict primary Epstein-Barr virus infection in B cells via IFN-γ

Oncotarget ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 6130-6141 ◽  
Author(s):  
Aurelia Jud ◽  
Monika Kotur ◽  
Christoph Berger ◽  
Claudine Gysin ◽  
David Nadal ◽  
...  
Keyword(s):  
B Cells ◽  
Virus Infection ◽  
Nk Cells ◽  
Epstein Barr Virus ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Barr Virus Infection

Interferon-gamma in a family with X-linked lymphoproliferative syndrome with acute Epstein-Barr virus infection

1989 ◽  
Vol 9 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Motohiko Okano ◽  
Geoffrey M. Thiele ◽  
Roger H. Kobayashi ◽  
Jack R. Davis ◽  
Mark S. Synovec ◽  
...  
Keyword(s):  
Virus Infection ◽  
Interferon Gamma ◽  
Epstein Barr Virus ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Lymphoproliferative Syndrome ◽  
Epstein Barr ◽  
Barr Virus Infection

Cytokine Gene Polymorphisms and Epstein-Barr Virus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3125-3125
Author(s):  
Ren Lin ◽  
Zhiping Fan ◽  
Ke Zhao ◽  
Qianli Jiang ◽  
Jing Sun ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Infection ◽  
Associated Diseases ◽  
Tnf Α ◽  
Cytokine Gene Polymorphisms ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Tgf Β1

Abstract Backgroud: Epstein-Barr virus (EBV) infection/reactivation and associated diseases remain common complications in recipients of HSCT, leading to severe end-organ diseases and malignance. Single nucleotide polymorphism (SNP) in cytokine genes is considered to be related with EBV-associated post-transplant lymphoproliferative disorders (PTLD) in solid-organ transplantation recipients. In this study, we analyzed the association between cytokine gene polymorphisms and EBV infection/reactivation or diseases in recipients undergoing allo-HSCT. Methods: A total of 233 patients who received allo-HSCT between March 2012 to December 2014 were enrolled in this study. Ten SNPs, including IL-1β -511 rs16944, IL-1RN +11100 rs315952, IL-2 -330 rs2069762, IL-4 -590 rs2243250, IL-10 -592 rs1800872, IL-12 +1188 rs3212227, TNF-α -308 rs1800629, TGF-β1-509 rs1800469, TGF-β1 +869 rs1800470, IFN-γ +874 rs2430561, were tested. The SNPs genotypes in patients with or without EBV infection/reactivation and associated diseases were compared. Besides, the risk factors for EBV infection/reactivation were studied. Results: Seventy-four patients developed EBV infection/reactivation. The patients with EBV infection/reactivation had higher frequencies of donor IL-1β -511 TT genotype, donor IL-4 -590 TT genotype and recipient TNF-α -308 GG genotype than those without (p=0.021, p=0.004, p=0.020, respectively) while the frequencies of donor IL-1β -511 CC genotype, donor IL-1RN +11100 TT genotype, donor IL-2 -330 TT genotype, donor IL-4 -590 CC genotype and recipient TNF-α-308 GA genotype in patients with EBV infection/reactivation were lower than those without (p=0.041, p=0.029, p=0.005, p=0.011, p=0.042, respectively). Multivariate analysis showed donor IL-4 -590TT genotype (p=0.016, HR=1.907, 95% CI =1.130-3.218) and recipient TNF-α -308GG genotype (p=0.002, HR=3.550, 95% CI=1.613-7.812) were risk factors for post-transplant EBV infection/reactivation while donor IL-1RN +11100TT genotype (p=0.001, HR=0.382, 95% CI=0.218-0.670) was protective factors for post-transplant EBV infection/reactivation. Twenty-one patients developed EBV-associated diseases. The patients who developed EBV-associated diseases had higher frequency of donor IFN-γ +874 AT genotype than those did not (p=0.027). On the contrary, the frequencies of donor IL-1β-511 CC genotype, donor IL-10 -592 AA genotype, donor IL-12 +1188 AA genotype and donor IFN-γ +874 AA genotype in patients with EBV-associated diseases were lower than those without (p=0.019, p=0.018, p=0.018, p=0.010, respectively). Conclusion: Several SNPs in cytokine genes might be associated with EBV infection/reactivation and the development of EBV-associated diseases in recipients of allo-HSCT. However, these association should be studied further. Disclosures No relevant conflicts of interest to declare.

Cytokine production and cytolytic mechanism of CD4+cytotoxic T lymphocytes in ex vivo expanded therapeutic Epstein-Barr virus–specific T-cell cultures

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3302-3309 ◽  
Author(s):  
Qi Sun ◽  
Robert L. Burton ◽  
Kenneth G. Lucas
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
T Cell ◽  
Cytotoxic T Lymphocytes ◽  
Epstein Barr Virus ◽  
Ex Vivo ◽  
Cd4 Cells ◽  
Barr Virus ◽  
Ifn Γ ◽  
Epstein Barr

Abstract Ex vivo expanded Epstein-Barr virus (EBV)–specific T cells have been successfully applied clinically for adoptive immunotherapy. However, the role of CD4+ T cells in the therapeutic T-cell culture has not been established for the reconstitution of EBV-specific immunity. We isolated and characterized CD4+ T-cell lines from the ex vivo T-cell cultures. Monoclonal line PD-F4 and oligoclonal lines ND-R4 and TD-B4 were CD3+CD4+CD8−. Cytolytic tests with targets of mismatched major histocompatibility complex (MHC) and anti-MHC antibodies confirmed that the cytotoxicity of these CD4+ cells was restricted by MHC class II. Single cells of ND-R4 expressed interferon-γ (IFN-γ, or interleukin 4 (IL-4), but rarely coexpressed these 2 cytokines. In contrast, PD-F4 coexpressed IFN-γ, IL-2, and IL-4. Kinetic studies with PD-F4 showed that expression of the 3 cytokines plateaued 5 hours upon stimulation and was then drastically reduced, with a pattern consistent with independent modulation and differential off-cycle signal requirements. The cytotoxicity of these CD4+ cells was largely resistant to brefeldin A, an inhibitor for cytolytic pathways by Fas-ligand family molecules. Although sensitive to concanamycin A and ethyleneglycotetraacetic acid, which inhibit cytotoxicity by granule exocytosis, the CD4+ cytotoxic T lymphocytes (CTLs) did not express perforin, suggesting a cytotoxic mechanism independent of perforin although involving exocytosis. Flow cytometric analysis showed that the CD4+ CTLs expressed granulysin, a recently identified cytolytic molecule associated with exocytotic cytolytic granules. These data suggested that CD4+ T cells in the therapeutic B-lymphoblastoid cell lines–primed T-cell culture are diverse in producing TH1 and TH2 cytokines, and may exert specific cytotoxicity via exocytosis of granulysin.

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