Selective inhibition of TNF-alpha induced cell adhesion molecule gene expression by tanapox virus.
Poxviruses encode virulence factors that have been identified as proteins that are secreted from infected host cells. Some of these secretory proteins impede host immune defences. We have previously demonstrated that tanapox virus (TPV) infected cells secrete an early 38 kDa glycopeptide that binds to human (h) interferon-gamma, hIL-2, and hIL-5. We now show an additional activity in the supernatant from TPV infected cells that down-regulates the expression of tumour necrosis factor-alpha (TNF-alpha) induced cell adhesion molecule gene expression. This activity was not detected in mock infected cells. Enzyme linked immunosorbent assays (ELISA) on primary human endothelial cells, show the induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) following TNF-alpha or IL-1 beta treatment, as expected. Supernatant from TPV infected cells significantly decreased the TNF-alpha but not IL-1 beta-induced expression of these molecules. Mobility shift assays and Northern blot analyses further show that the supernatant from TPV infected cells inhibited TNF-alpha-induced activation of the nuclear transcription factor-kappa B (NF-kappa B) and transcriptional activation of the E-selectin, VCAM-1 and ICAM-1 genes. Based on TNF-alpha affinity chromatography, this activity appears to be associated with a 38 kDa glycopeptide.
Paulose
M
M
Department of Biological Sciences, Western Michigan University, Kalamazoo 49008, USA.
Bennett
B L
BL
Manning
A M
AM
Essani
K
K
D000818:Animals; D016645:Aotidae; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D018158:Yatapoxvirus / Q000276:immunology / Q000472:pathogenicity*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1