title: Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.
abstract: Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.
authors.affiliation: Centro de Biologia Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas-Universidad Autonoma de Madrid), 28049 Madrid, Spain.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Pontejo
authors.affiliation: Centro de Investigacion en Sanidad Animal (Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria), 28130 Valdeolmos, Madrid, Spain.
authors.forename: Ali
authors.initials: A
authors.lastname: Alejo
authors.affiliation: Centro de Biologia Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas-Universidad Autonoma de Madrid), 28049 Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcami
mesh_terms: D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D011212:Poxviridae / Q000276:immunology* / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins