scholarly journals Endosomal Toll-Like Receptors (TLRs) mediate enhancement of IL-17A production triggered by Epstein-Barr virus (EBV) DNA in mice

2018 ◽  
Vol 12 (02.1) ◽  
pp. 26S
Author(s):  
Marwa Shehab ◽  
Rana Jammaz ◽  
Noor Salloum ◽  
Elias A. Rahal

Introduction: EBV has long-been associated with autoimmune disorders. We have previously demonstrated that EBV DNA increases the production of IL-17A in mice. This property may play a role in the association of EBV with autoimmune diseases. The objective of this study was to elucidate mechanisms through which EBV DNA modulates IL-17A levels in mice. Methodology: To study the potential role of endosomal receptors in detecting EBV DNA, chloroquine, an endosomal maturation inhibitor, was used to treat mouse peripheral blood mononuclear cells (PBMCs) in the presence or absence of EBV DNA. IL-17A levels were then assessed by ELISA. Subsequently, to determine whether TLR3, 7 or 9 played a role in this pathway, specific inhibitors were used for these TLRs both in mouse PBMCs and in vivo in BALB/c mice treated with the viral DNA; IL-17A levels were then similarly assessed. Results: IL-17A production was enhanced from mouse PBMCs cultured with EBV DNA; pre-incubation of PBMCs with chloroquine significantly reduced its production. When cells were cultured with EBV DNA and a TLR3, 7 or 9 inhibitor, a significant decrease in IL-17A levels was detected. A similar decrease in the EBV DNA-triggered IL-17A production in mice was observed when animals were treated with the TLR inhibitors. Conclusion: Endosomal TLRs appear to be involved in recognizing EBV DNA and subsequently triggering IL-17A production in mice. Targeting these receptors in EBV positive subjects with autoimmunity may be useful pending investigations assessing whether they play a similar role in humans.

PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 964-967
Author(s):  
THOMAS J. BOWEN ◽  
RALPH J. WEDGWOOD ◽  
HANS D. OCHS ◽  
WERNER HENLE

In vivo and in vitro humoral and cellular immune responses were studied in a 2½-year-old girl immediately before, during, and after an asymptomatic infection with Epstein-Barr virus. During the acute EBV infection, the patient's peripheral blood mononuclear cells were deficient in immunoglobulin synthesis and suppressed the in vitro immunoglobulin synthesis of normal allogeneic cells. In vitro mitogen transformation of lymphocytes was reduced. In vivo antibody responses to the T cell-dependent antigens bacteriophage φX 174 and Keyhole limpet hemocyanin were markedly depressed. These studies suggest that suppressor cells induced during acute EBV infection not only suppress immunoglobulin synthesis in vitro, but also interfere with in vivo antibody synthesis.


2019 ◽  
Vol 57 (5) ◽  
pp. 759-765 ◽  
Author(s):  
Wang Kedi ◽  
Xu Dongjiang ◽  
Lv Zhi ◽  
Gao Yan ◽  
Jia Kun ◽  
...  

Abstract Background Epstein-Barr virus (EBV) DNA load monitoring in blood is essential for the diagnosis of EBV-associated diseases. However, the best-suited blood compartment for detection is still under discussion. The aim of this study was to evaluate the diagnostic value of EBV-DNA load in peripheral blood mononuclear cells (PBMC), plasma and whole blood (WB) samples. Methods A total of 156 patients, including 45 patients with infectious mononucleosis (IM), 57 patients with EBV-associated hemophagocytic lymphohistiocytosis (HLH) and 54 patients with post-transplant lymphoproliferative disorders (PTLD), were enrolled in this study. The EBV-DNA load in PBMC, plasma and WB samples were measured with real-time quantitative polymerase chain reaction (PCR). Results EBV-DNA load of patients with HLH showed no statistical difference in PBMC, plasma and WB samples, while patients with IM and PTLD showed a higher viral load in PBMC samples. The strongest correlation of EBV-DNA level was found between PBMC and WB samples among patients with IM, HLH and PTLD. The follow-up of EBV-DNA showed that the viral load became negative along with the recovery from the disease, while that in WB and PBMC would remain positive for a long time. Conclusions For the diagnosis and monitoring of EBV-DNA, the type of specimen should be chosen reasonably according to the disease. As for IM and HLH, plasma is recommended to quantify the EBV-DNA load, while PBMC and plasma are preferred in PTLD.


Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 172-177 ◽  
Author(s):  
N Yoneda ◽  
E Tatsumi ◽  
M Kawanishi ◽  
K Teshigawara ◽  
S Masuda ◽  
...  

Abstract Epstein-Barr virus (EBV) DNA was detected in polyclonal T cells that proliferated transiently in a 21-year-old male (referred to as H.J.) who underwent an apparently benign lymphocytosis (white blood cells, 31 x 10(6)/microL; lymphocyte, 79%) with fever, tonsillar swelling, lymphadenopathy, and hepatosplenomegaly. The symptoms and signs subsided mostly within a month of hospitalization. The major population of the lymphocytes at admission was positive for CD3, CD8 (4/8 ratio, 0.16), WT31, and DR antigen. Eight percent of the leukocytes were too blastoid to be classified as atypical lymphocytes of infectious mononucleosis (IM). The blastoid lymphocytes and the duration and degree of the lymphocytosis and hypergammaglobulinemia appeared inconsistent with IM, whereas the EBV serology indicated either EBV primary infection or a secondary alteration of normal seropositive EBV immunity. The genomic analysis of T-cell receptor beta chain in the peripheral blood mononuclear cells (PBMC) at admission with a C beta probe did not show a monoclonal rearrangement. EBV genome was detected in these cells, using the BamHI W and K probe, but not in the cells after discharge. Analysis of the EBV terminal repeat junctional sequence, using Xho I fragment of the latent membrane protein (LMP) probe binding with the terminus, did not show monoclonal or oligoclonal populations. EBV-associated nuclear antigen (EBNA) was detected in 36% of the PBMC at admission, but not in the later cells. These EBNA- positive cells were found to form rosette with sheep erythrocytes. The PBMC of six acute IM patients contained neither EBV DNA nor EBNA- positive cells. The observations in this case show a unique type of EBV infection in T cells that has not been previously reported.


Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 172-177 ◽  
Author(s):  
N Yoneda ◽  
E Tatsumi ◽  
M Kawanishi ◽  
K Teshigawara ◽  
S Masuda ◽  
...  

Epstein-Barr virus (EBV) DNA was detected in polyclonal T cells that proliferated transiently in a 21-year-old male (referred to as H.J.) who underwent an apparently benign lymphocytosis (white blood cells, 31 x 10(6)/microL; lymphocyte, 79%) with fever, tonsillar swelling, lymphadenopathy, and hepatosplenomegaly. The symptoms and signs subsided mostly within a month of hospitalization. The major population of the lymphocytes at admission was positive for CD3, CD8 (4/8 ratio, 0.16), WT31, and DR antigen. Eight percent of the leukocytes were too blastoid to be classified as atypical lymphocytes of infectious mononucleosis (IM). The blastoid lymphocytes and the duration and degree of the lymphocytosis and hypergammaglobulinemia appeared inconsistent with IM, whereas the EBV serology indicated either EBV primary infection or a secondary alteration of normal seropositive EBV immunity. The genomic analysis of T-cell receptor beta chain in the peripheral blood mononuclear cells (PBMC) at admission with a C beta probe did not show a monoclonal rearrangement. EBV genome was detected in these cells, using the BamHI W and K probe, but not in the cells after discharge. Analysis of the EBV terminal repeat junctional sequence, using Xho I fragment of the latent membrane protein (LMP) probe binding with the terminus, did not show monoclonal or oligoclonal populations. EBV-associated nuclear antigen (EBNA) was detected in 36% of the PBMC at admission, but not in the later cells. These EBNA- positive cells were found to form rosette with sheep erythrocytes. The PBMC of six acute IM patients contained neither EBV DNA nor EBNA- positive cells. The observations in this case show a unique type of EBV infection in T cells that has not been previously reported.


2020 ◽  
Vol 66 (9) ◽  
pp. 1219-1227
Author(s):  
Bin Hu ◽  
Ming Sun ◽  
Zijin Wang ◽  
Yanping Zheng ◽  
Weifeng Cai ◽  
...  

Abstract Background Epstein–Barr virus (EBV) infection has a role in the development and progression of nasopharyngeal carcinoma (NPC); however, it is unclear whether EBV load correlates with tumor prognosis or the need for immunotherapy. This study evaluated whether the EBV DNA concentration in peripheral blood mononuclear cells (PBMC) or programmed cell death-ligand1 (PD-L1) expression in tumor-infiltrating lymphocytes (TIL) could predict the clinical outcomes of patients with NPC. Methods Clinicopathological parameters of 198 patients with NPC were analyzed retrospectively from June 2012 to May 2018. Patients’ EBV loads were determined by droplet digital PCR. TIL PD-L1 was analyzed by immunohistochemistry. Results A log value of 1.98 log IU/mL for PBMC EBV DNA and a percentage of PD-L1 expression of 15% in TILs marked distinguishing cutoffs in NPC prognosis. The 5-year progression-free survival (PFS) rates in patients with high vs low log (PBMC EBV DNA) were 68.2% and 93.1%, respectively (P = 0.002). The 5-year PFS rates in patients with high vs low TIL PD-L1 expression were 66.3% and 33.7%, respectively (P = 0.03). The 5-year PFS rates of the high-risk group (high log [PBMC EBV DNA] and low TIL PD-L1), low-risk group (low log [PBMC EBV DNA] and high TIL PD-L1), and those in between (intermediate group) were 0%, 91.9%, and 71.4%, respectively (P < 0.001). Conclusion Concentrations of PBMC EBV DNA and TIL PD-L1 expression can be used as prognostic markers in NPC. The combination of both an increased EBV DNA concentration and suppressed TIL PD-L1 expression is associated with metastasis or relapse.


2014 ◽  
Vol 66 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Ana Banko ◽  
Ivana Lazarevic ◽  
M. Folic ◽  
Maja Cupic ◽  
Tanja Jovanovic

The development of nasopharyngeal carcinoma (NPC) is the result of interaction between Epstein-Barr Virus (EBV) and many non-viral factors. The aims of this study were to determine the prevalence of EBV in NPC biopsies from Serbian patients and to investigate the correlation between EBV presence and demographic, anamnestic and clinical data. Ninety-three tissue blocks were included. For detection of EBV DNA, the C terminus of the LMP1 gene was amplified by nested-PCR. Twenty-eight biopsies were EBV-DNA-positive (30.1%), with a statistically significant difference in EBV DNA presence between geographical regions (p=0.02) and between the stages of tumor-node-metastasis (TNM) (p=0.02). A correlation was also found with the presence of EBV DNA and smoking (p=0.02). The correlation of EBV DNA presence, with or without smoking and the promising outcome of the disease was statistically significant (p=0.02; p=0.01). The EBV DNA findings from this study confirm the role of EBV in NPC carcinogenesis, and show the different distribution among TNM stages and correlation between the virus and outcome of disease.


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Zhongbin Xia ◽  
Fanru Meng ◽  
Ying Liu ◽  
Yuxuan Fang ◽  
Xia Wu ◽  
...  

Background: Rheumatoid arthritis (RA) is a inflammatory disease that characterized with the destruction of synovial joint, which could induce disability. Inflammatory response mediated the RA. It has been reported that MiR-128-3p is significantly increased in RA, while the potential role was still unclear. Methods: T cells in peripheral blood mononuclear cell (PBMC) were isolated from the peripheral blood from people of RA and normal person were used. Real-time PCR was performed to detect the expression of MiR-128-3p, while the protein expression of tumor necrosis factor-α-induced protein 3 (TNFAIP3) was determined using Western blot. The levels of IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). The expression of CD69 and CD25 was detected using flow cytometry. The RA mouse model was constructed for verification of the role of MiR-128-3p. Results: The expression of MiR-128-3p was significantly increased, while TNFAIP3 was decreased, the levels of IL-6 and IL-17 were also increased in the T cells of RA patients. Down-regulated MiR-128-3p significantly suppressed the expression of p-IkBα and CD69, and CD25in T cells. MiR-128-3p targets TNFAIP3 to regulate its expression. MiR-128-3p knockdown significantly suppressed the activity of nuclear factor κB (NF-κB) and T cells by up-regulating TNFAIP3, while cells co-transfected with si-TNFAIP3 abolished the effects of MiR-128-3p knockdown. The in vivo experiments verified the potential role of MiR-128-3p on RA. Conclusion: Down-regulated MiR-128-3p significantly suppressed the inflammation response of RA through suppressing the activity of NF-κB pathway, which was mediated by TNFAIP3.


PEDIATRICS ◽  
1995 ◽  
Vol 96 (4) ◽  
pp. 783-785
Author(s):  
Tetsuo Hashida ◽  
Emiko Komura ◽  
Maki Yoshida ◽  
Takuji Otsuka ◽  
Shigeyoshi Hibi ◽  
...  

Human herpesvirus-7 (HHV-7), a newly identified lymphotropic member of the herpes family, has recently been isolated from the peripheral blood mononuclear cells (PBMC) of healthy individuals.1 Similar to human herpesvirus-6 (HHV-6), HHV-7 has been found to prevalently infect children at younger ages.2-4 HHV-6 is known to be a causative agent of exanthema subitum,5 and has also been identified in cases of fatal fulminant hepatitis,6 hemophagocytic syndrome,7 encephalitis,8 and intussusception.9 Moreover, HHV-6 infection with severe consequences has been reported in bone marrow and organ transplant patients undergoing immunosuppressive therapy.10-12 Although HHV-7 has recently been isolated from the PBMC of the patients with chronic fatigue syndrome13 and of a child with symptoms mimicking chronic Epstein Barr virus (EBV) infection,14 it is as yet unknown what other diseases are associated with this newly isolated HHV-7 virus infection.


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