Local production of tumor necrosis factor encoded by recombinant vaccinia virus is effective in controlling viral replication in vivo.

Sambhi, Sharan K.; Kohonen‐Corish, Maija; Ramshaw, Ian A.

doi:10.1073/pnas.88.9.4025

Cited by 89 publications

(62 citation statements)

References 38 publications

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“…However, our studies also indicated that IFN~: is not the only cytokine involved in virus clearance from salivary glands. The search for such a cytokine focused on TNF~, which has been implicated in a number of parasitic (Havell, 1987;Titus et al, 1989;Chen et al, 1992;Johnson, 1992;Silva & Faccioli, 1992), viral (Rossol-Voth et aI., 1991Sambhi et al, 1991) and bacterial infections (Nauciel & Espinase-Maes, 1992). TNF~ is a pluripotent cytokine with a variety of biological properties and is produced by many cell types, but mostly by activated macrophages (Larrick & Wright, 1990).…”

Section: Discussionmentioning

confidence: 99%

Participation of endogenous tumour necrosis factor in host resistance to cytomegalovirus infection

Pavić

Polić

Crnković

et al. 1993

Journal of General Virology

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Interferon gamma (IFNT) represents an essential cytokine involved in murine cytomegalovirus (MCMV) clearance from the salivary gland and the control of horizontal transmission. Because IFN 7 cannot be responsible for all cytokine effects during recovery from MCMV infection we have now tested the potential participation of tumour necrosis factor alpha (TNFct) in the antiviral defence. Neutralization of endogenous TNF~ abolished the antiviral activity of CD4 T cells in immunocompetent as well as in CD8 subset-deficient mice. These data suggest that the antiviral effect of the CD4 subset requires the presence of at least two cytokines, namely IFN7 and TNF~. Depletion of endogenous TNF~ in adoptive cell transfer recipients diminished the antiviral function of CD8 T lymphocytes suggesting that TNFct also participates in CD8 T cell effector functions. Furthermore, endogenous cytokines were found to be required for survival after infection with lethal doses of MCMV, whereas immunotherapy with recombinant TNF~ and IFN~ could not limit virus replication in vivo. The results suggest that, similar to IFNy, TNFct is an integral part of the protective mechanisms involved in cytomegalovirus clearance.

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Section: Discussionmentioning

confidence: 99%

Participation of endogenous tumour necrosis factor in host resistance to cytomegalovirus infection

Pavić

Polić

Crnković

et al. 1993

Journal of General Virology

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“…TNF is directly cytotoxic to cells infected with both DNA and RNA viruses (29,30), and overexpression of the cytokine by a recombinant vaccinia virus leads to rapid virus clearance from infected mice (31). The TNF superfamily of cytokines and receptors can activate nuclear factor B and effect cell growth, differentiation, or death.…”

Section: Hcv Core Protein Inhibits Tnf-␣-induced Cleavage Of Poly-(admentioning

confidence: 99%

Inhibition of Tumor Necrosis Factor (TNF-α)-mediated Apoptosis by Hepatitis C Virus Core Protein

Ray¹,

Meyer²,

Steele³

et al. 1998

Journal of Biological Chemistry

220

140

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Hepatitis C virus (HCV) putative core protein has displayed many intriguing biological properties. Since tumor necrosis factor (TNF) plays an important role in controlling viral infection, in this study the effect of the core protein was investigated on the TNF-␣ induced apoptosis of human breast carcinoma cells (MCF7). HCV core protein when expressed inhibited TNF-␣-induced apoptotic cell death unlike the control MCF7 cells, as determined by cell viability and DNA fragmentation analysis. Additionally, HCV core protein blocked the TNF-induced proteolytic cleavage of the death substrate poly(ADP-ribose) polymerase from its native 116-kDa protein to the characteristic 85-kDa polypeptide. Results from this study suggest that the HCV core protein plays a role in the inhibition of TNF-␣-mediated cell death. Thus, the ability of core protein to inhibit the TNF-mediated apoptotic signaling pathway may provide a selective advantage for HCV replication, allowing for evasion of host antiviral defense mechanisms. Hepatitis C virus (HCV)1 is an important cause of morbidity and mortality worldwide, causing a spectrum of liver disease ranging from an asymptomatic carrier state to end-stage liver disease. The most important feature of persistent HCV infection is the development of chronic hepatitis in half of the infected individuals and the potential for disease progression to hepatocellular carcinoma (1). Unfortunately, a number of important issues related to HCV-mediated disease progression is unknown at this time. An HCV genome contains a linear, positive-strand RNA molecule of ϳ9,500 nucleotides encoding a single polyprotein precursor of ϳ3,000 amino acids (2). The polyprotein is cleaved by both host and viral proteases (3, 4) to generate three putative structural proteins (core, E1, and E2) and at least six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B). The genomic region encoding the putative core protein is located between amino acids 1-191. HCV core protein may be the fundamental unit for the encapsidation of genomic RNA to facilitate virus morphogenesis.However, in vitro studies suggest that the HCV core protein has many additional biological properties. The core protein transactivates the human c-myc proto-oncogene and unrelated viral promoters and suppresses c-fos, p53, and human immunodeficiency virus type 1 long terminal repeat promoter activities (5-7). HCV core protein transforms primary rat embryo fibroblasts in association with a cooperative oncogene to a tumorigenic phenotype (8), interacts with the lymphotoxin-␤ receptor to possibly modulate immune function (9), and associates with apolipoprotein II for a potential role on lipid metabolism (10). A recent study (11) suggests that missense mutations in the clustering variable region of the hydrophilic domain (residues 39 -76) of the core gene may be involved in the pathogenesis of chronic HCV infection during hepatocellular carcinogenesis.Viral infections may often induce an apoptotic response as a defense mechanism in host cells, and many vir...

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“…One of the cytokines secreted by macrophages is TNF-␣. This cytokine plays a beneficial role in clearance of a number of viral infections (2)(3)(4)(5) as well as parasitic and bacterial infections (6 -10). In contrast, TNF-␣ is also involved in the immunopathology of diseases such as diabetes, hepatitis, and rheumatoid arthritis (11)(12)(13)(14).…”

mentioning

confidence: 99%

Expression of TNF-α by Herpes Simplex Virus-Infected Macrophages Is Regulated by a Dual Mechanism: Transcriptional Regulation by NF-κB and Activating Transcription Factor 2/Jun and Translational Regulation Through the AU-Rich Region of the 3′ Untranslated Region

Paludan

Ellermann-Eriksen

Kruys

et al. 2001

The Journal of Immunology

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Here we have investigated the regulation of TNF-α expression in macrophages during HSV-2 infection. Despite a low basal level of TNF-α mRNA present in resting macrophages, no TNF-α protein is detectable. HSV-2 infection marginally increases the level of TNF-α mRNA and protein in resting macrophages, whereas a strong increase is observed in IFN-γ-activated cells infected with the virus. By reporter gene assay it was found that HSV infection augments TNF-α promoter activity. Moreover, treatment of the cells with actinomycin D, which totally blocked mRNA synthesis, only partially prevented accumulation of TNF-α protein, indicating that the infection lifts a block on translation of TNF-α mRNA. EMSA analysis showed that specific binding to the κB#3 site of the murine TNF-α promoter was induced within 1 h after infection and persisted beyond 5 h where TNF-α expression is down-modulated. Binding to the cAMP responsive element site was also induced but more transiently with kinetics closely following activation of the TNF-α promoter. Inhibitors against either NF-κB activation or the activating transcription factor 2 kinase p38 abrogated TNF-α expression, showing a requirement for both signals for activation of the promoter. This observation was corroborated by reporter gene assays. As to the translational regulation of TNF-α, the AU-rich sequence in the 3′ untranslated region of the mRNA was found to be responsible for this control because deletion of this region renders mRNA constitutively translationable. These results show that TNF-α production is induced by HSV-2 in macrophages through both transcriptional and translational regulation.

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Local production of tumor necrosis factor encoded by recombinant vaccinia virus is effective in controlling viral replication in vivo.

Cited by 89 publications

References 38 publications

Participation of endogenous tumour necrosis factor in host resistance to cytomegalovirus infection

Participation of endogenous tumour necrosis factor in host resistance to cytomegalovirus infection

Inhibition of Tumor Necrosis Factor (TNF-α)-mediated Apoptosis by Hepatitis C Virus Core Protein

Expression of TNF-α by Herpes Simplex Virus-Infected Macrophages Is Regulated by a Dual Mechanism: Transcriptional Regulation by NF-κB and Activating Transcription Factor 2/Jun and Translational Regulation Through the AU-Rich Region of the 3′ Untranslated Region

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