Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation

doi:10.1016/0092-8674(94)90005-1

Cell

Volume 79, Issue 7, 30 December 1994, Pages 1137-1146

https://doi.org/10.1016/0092-8674(94)90005-1 Get rights and content

Abstract

Nitric oxide (NO) produced by murine macrophages is important in murine resistance to ectromelia virus, herpes simplex virus, and vaccinia virus infection. In contrast, NO production by human mononuclear cells has been difficult to demonstrate, and a role for NO in human responses to infection is uncertain. We report constitutive, low level, macrophage-type NO synthase (iNOS) expression in Epstein-Barr virus (EBV)-transformed human B lymphocytes and Burkitt's lymphoma cell lines. Immune NOS activity is involved in maintaining EBV latency through down-regulation of the expression of the immediate-early EBV transactivator Zta. NO also inhibits apoptosis in B lymphocyte cell lines. The effects of NO are largely independent of cGMP and influential on signaling pathways regulated by (sulfhydryl) redox status. These results suggest that NO plays a physiological role in human B cell biology by inhibiting programmed cell death and maintaining viral latency.

References (78)

J.E. Albina et al.
Suppression of lymphocyte proliferation through the nitric oxide synthesizing pathway
J. Surg. Res.
(1991)
C. Alfieri et al.
Early events in Epstein-Barr virus infection of human B lymphocytes
Virology
(1991)
M.M. Bradford
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding
Anal. Biochem.
(1976)
D.D. Duncan et al.
Differential lymphocyte growth-modifying effects of oxidants: changes in cytosolic Ca⁺²
Toxicol. Appl. Pharmacol.
(1989)
B.M. Freed et al.
Inhibition of interleukin-2 production in the human T cell line JURKAT by nonpolar maleimides
Toxicol. Appl. Pharmacol.
(1991)
R. Gopalakrishna et al.
Nitric oxide and nitric oxide-generating agents induce a reversible inactivation of protein kinase C activity and phorbol ester binding
J. Biol. Chem.
(1993)
D.L. Granger
Macrophage production of nitrogen oxides in host defence against microorganisms
Res. Immunol.
(1991)
S.S. Gross et al.
Tetrahydrobiopterin synthesis
An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle
J. Biol. Chem.
(1992)
S.S. Gross et al.
Macrophage and endothelial cell nitric oxide synthesis: cell-type selective inhibition by N^g-aminoarginine, N^g-nitroarginine and N^g-methylarginine
Biochem. Biophys. Res. Commun.
(1990)
S. Henderson et al.
Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death
Cell
(1991)

J. Hibbs

Synthesis of nitric oxide from l-arginine: a recently discovered pathway induced by cytokines with antitumour and antimicrobial activity

Res. Immunol.

(1991)

D.M. Hockenbery et al.

Bcl-2 functions in an antioxidant pathway to prevent apoptosis

Cell

(1993)

S.J. Kirk et al.

Cloned murine T lymphocytes synthesize a molecule with the biological characteristics of nitric oxide

Biochem. Biophys. Res. Commun.

(1990)

M. Kishishita et al.

Production of monoclonal antibody to a late intracellular Epstein-Barr virus-induced antigen

Virology

(1984)

C.D. Laherty et al.

The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B.

J. Biol. Chem.

(1992)

S. Mohr et al.

Mechanism of covalent modification of glyceraldehyde 3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite, and related nitrosating agents

FEBS Lett.

(1994)

L. Molina y Vedia et al.

Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation

J. Biol. Chem.

(1992)

C.F. Nathan et al.

Role of nitric oxide synthesis in macrophage antimicrobial activity

Curr. Opin. Immunol.

(1991)

C.F. Nathan et al.

Regulation of the biosynthesis of nitric oxide

J. Biol. Chem.

(1994)

C.F. Nathan et al.

Nitric oxide synthases: roles, tolls, and controls

Cell

(1994)

R. Radi et al.

Peroxynitrite oxidation of sulfhydryls

The cytotoxic potential of superoxide and nitric oxide

J. Biol. Chem.

(1991)

Z. Rozsnyay et al.

Phenylarsine oxide (PAO) blocks antigen receptor-induced calcium response and tyrosine phosphorylation of a distinct group of proteins

Immunol. Lett.

(1993)

M. Sarih et al.

Nitric oxide synthase induces macrophage death by apoptosis

Biochem. Biophys. Res. Commun.

(1993)

R. Schreck et al.

A role for oxygen radicals as second messengers

Trends Cell Biol.

(1991)

J.S. Stamler

Redox signaling: nitrosylation and related target interactions of nitric oxide

Cell

(1994)

C. Abate et al.

Redox regulation of fos and jun DNA-binding activity in vitro

Science

(1990)

K. Asano et al.

Constitutive and inducible nitric oxide synthase gene expression, activity and regulation in human lung epithelial cells

A. Bannister et al.

In vitro DNA binding activity of Fos/Jun and BZLF1 but not $C EBP$ is affected by redox changes

Oncogene

(1991)

J.S. Beckman et al.

Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide

V.M. Bolotina et al.

Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle

Nature

(1994)

A. Calender et al.

Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells

M.L. Cameron et al.

Human alveolar and peritoneal macrophages mediate fungistasis independently of l-arginine oxidation to nitrite or nitrate

Am. Rev. Respir. Dis.

(1990)

A. Chevallier-Greco et al.

Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter

EMBO J.

(1986)

J.D. Crapo et al.

Signalling by non-receptor surface-mediated surface active biomolecules

J. Clin. Invest.

(1994)

K.D. Croen

Evidence for antiviral effect of nitric oxide

Inhibition of herpes

J. Clin. Invest.

(1993)

M. Daibata et al.

Activation of latent EBV via anti-IgG-triggered, second messenger pathways in the Burkitt's lymphoma cell line Akata

J. Immunol.

(1990)

M. Denis

Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates

J. Leukocyt. Biol.

(1991)

P.J. Farrell et al.

Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos

EMBO J.

(1989)

E. Flemington et al.

Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1

J. Virol.

(1990)

Cited by (461)

A fluorogenic nitric oxide donor induced by yellow LED light for cells proliferation inhibition and imaging
2024, Nitric Oxide - Biology and Chemistry
Nitric oxide (NO), as a vital cellular signalling molecule in physiological processes, has been found to play an important role in various biological functions. In this study, we rationally designed three NO donors by tethering nitrobenzene derivatives to three fluorescent chromophores. NX-NO was found to release NO and exhibit a high fluorescence turn-on signal ratio upon exposure to LED yellow light. Additionally, it had excellent photo-stability and good inhibitory activity against cancer cell proliferation, and was successfully applied to cell imaging. Moreover, we detected the release of NO and fluorescence response in the blood of a mouse, suggesting its potential therapeutic application in living organisms.
Low vitamin D exposure and risk of nasopharyngeal carcinoma: Observational and genetic evidence from a multicenter case–control study
2021, Clinical Nutrition
Little is known about the risk of nasopharyngeal carcinoma (NPC) in relation to vitamin D exposure. The aim of this study was to examine the associations of NPC risk with serum level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD, and potential effect modification by several putative risk factors of NPC.
Our multicenter case–control study in Hong Kong recruited 815 NPC cases and 1502 frequency-matched (by sex and age) hospital controls from five major regional hospitals, and recruited 299 healthy subjects from blood donation centers (2014–2017). Circulating level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD (rs12785878, rs11234027, rs12794714, rs4588 and rs6013897) were measured by validated enzyme immunoassay and the iPLEX assay on the MassARRAY System, respectively. Data were also collected on demographics, lifestyle factors, ultraviolet radiation exposure, and potential confounders using a computer-assisted, self-administered questionnaire with satisfactory test-retest reliability. Unconditional logistic regression models were used to estimate ORs and 95% CIs.
Despite no significant association of NPC risk with circulating 25OHD and genetic predicted 25OHD, there was evidence for an inverse association in participants with normal body mass index (between 18.5 and 27.5) across categories of 25OHD (P_trend = 0.003), and a positive association in those with low socioeconomic status across categories based on the genetic score (P_trend = 0.005). In addition, risk of NPC diagnosed at an early stage was higher for genetically lower 25OHD level (adjusted OR = 3.09, 95% CI = 1.04–9.21, P_trend = 0.022).
Findings of this first comprehensive study to investigate the positive association of NPC risk with vitamin D deficiency need to be confirmed and be best interpreted with results of further similar studies. Our findings may inform possible etiological mechanisms of the associations with several putative risk/protective factors of NPC.
Toll-like receptor (TLR)4 signalling induces myeloid differentiation primary response gene (MYD) 88 independent pathway in avian species leading to type I interferon production and antiviral response
2018, Virus Research
Engagement of toll-like receptor (TLR)4 ligand, lipopolysaccharide (LPS) with TLR4 in mammals activates two downstream intracellular signaling routes; the myeloid differentiation primary response gene (MyD)88 dependent and independent pathways. However, existence of the later pathway leading to production of type I interferons (IFNs) in avian species has been debated due to conflicting observations. The objective of our study was to investigate whether LPS induces type I IFN production in chicken macrophages leading to antiviral response attributable to type I IFN. We found that LPS elicits type I IFN response dominated by IFN-β production. We also found that reduction in infectious laryngotracheitis virus (ILTV) replication by LPS-mediated antiviral response is attributable to type I IFNs in addition to nitric oxide (NO). Our findings imply that LPS elicits both MyD88 dependent and independent pathways in chicken macrophages consequently eliciting anti-ILTV response attributable to production of both type I IFNs and NO.
Progressive loss of nigrostriatal dopaminergic neurons induced by inflammatory responses to fipronil
2016, Toxicology Letters
Inflammatory responses are involved in mechanisms of neuronal cell damage in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD). We investigated the mechanisms whereby inflammatory responses contribute to loss of dopaminergic neurons in fipronil (FPN)-treated rats. After stereotaxic injection of FPN in the substantia nigra (SN), the number of tyrosine hydroxylase (TH)-positive neurons and the levels of TH expression in the SN decreased at 7 days, and a significant decrease was observed at 14 days with a subsequent reduction in striatal TH expression. Decreases in dopamine (DA) levels, however, began at 3 days post-injection, preceding the changes in TH expression. In contrast, glial fibrillary acidic protein (GFAP) expression was significantly increased at 3 days and persisted for up to 14 days post-lesion; these changes in GFAP expression appeared to be inversely correlated with TH expression. Furthermore, we found that FPN administration induced an inflammatory response characterized by increased levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), which was mediated by activated microglia following infusion of FPN unilaterally into the SN. Intranigral injection of FPN underwent an inflammatory response with a resultant ongoing loss of dopaminergic neurons, indicating that pesticides may have important implication for the study of PD.
A review of fibropapillomatosis in Green turtles (Chelonia mydas)
2016, Veterinary Journal
Despite being identified in 1938, many aspects of the pathogenesis and epidemiology of fibropapillomatosis (FP) in marine turtles are yet to be fully uncovered. Current knowledge suggests that FP is an emerging infectious disease, with the prevalence varying both spatially and temporally, even between localities in close proximity to each other. A high prevalence of FP in marine turtles has been correlated with residency in areas of reduced water quality, indicating that there is an environmental influence on disease presentation.
Chelonid herpesvirus 5 (ChHV5) has been identified as the likely aetiological agent of FP. The current taxonomic position of ChHV5 is in the family Herpesviridae, subfamily Alphaherpesvirinae, genus Scutavirus. Molecular differentiation of strains has revealed that a viral variant is typically present at specific locations, even within sympatric species of marine turtles, indicating that the disease FP originates regionally. There is uncertainty surrounding the exact path of transmission and the conditions that facilitate lesion development, although recent research has identified atypical genes within the genome of ChHV5 that may play a role in pathogenesis. This review discusses emerging areas where researchers might focus and theories behind the emergence of FP globally since the 1980s, which appear to be a multi-factorial interplay between the virus, the host and environmental factors influencing disease expression.
Innate Cytokine Responses and Their Functions during Viral Infections
2016, Encyclopedia of Immunobiology
Innate cytokines are soluble mediators produced by a wide range of cells including innate immune and even nonimmune cells. Once engaged, specialized sensors recognizing molecular structures uniquely expressed during infection, stimulate production of innate cytokines and downstream cascade responses. During viral infections, type I interferons (IFNs) play important direct roles in early antiviral defense. Together with other innate cytokines, they also deliver immunoregulatory functions to help orchestrate inflammation, defense delivered by innate immune cells such as natural killer (NK) cells and conditions promoting adaptive immune responses. When production continues through times of overlapping innate and escalating adaptive immunity, innate cytokines regulate CD8 T cell effector responses, and long-term production balances viral clearance as compare to chronic infection with interleukin-6 (IL-6) enhancing but type I IFNs inhibiting clearance. Thus, the complex and sometimes contradictory functions assigned to innate cytokines are context dependent. During acute infections, the biological consequences of NK and CD8 T cell exposure to type I IFNs are shaped by flexibility in use of the signal transducers and activators of transcription, STAT1 and STAT4. Key known and unknown steps regulated by innate cytokines, during evolving immune responses to viral infections, are reviewed in this article.

View all citing articles on Scopus

View full text

Cell

ArticleNitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation

Abstract

J. Surg. Res.

Virology

Anal. Biochem.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

J. Biol. Chem.

Res. Immunol.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Cell

Res. Immunol.

Cell

Biochem. Biophys. Res. Commun.

Virology

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Curr. Opin. Immunol.

J. Biol. Chem.

Cell

J. Biol. Chem.

Immunol. Lett.

Biochem. Biophys. Res. Commun.

Trends Cell Biol.

Cell

Redox regulation of fos and jun DNA-binding activity in vitro

Science

Constitutive and inducible nitric oxide synthase gene expression, activity and regulation in human lung epithelial cells

In vitro DNA binding activity of Fos/Jun and BZLF1 but not CEBP is affected by redox changes

Oncogene

Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide

Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle

Nature

Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells

Human alveolar and peritoneal macrophages mediate fungistasis independently of l-arginine oxidation to nitrite or nitrate

Am. Rev. Respir. Dis.

Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter

EMBO J.

Signalling by non-receptor surface-mediated surface active biomolecules

J. Clin. Invest.

Evidence for antiviral effect of nitric oxide

Inhibition of herpes

J. Clin. Invest.

Activation of latent EBV via anti-IgG-triggered, second messenger pathways in the Burkitt's lymphoma cell line Akata

J. Immunol.

Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates

J. Leukocyt. Biol.

Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos

EMBO J.

Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1

J. Virol.

Article
Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation

In vitro DNA binding activity of Fos/Jun and BZLF1 but not $C EBP$ is affected by redox changes