Paulose M, Bennett B L, Manning A M, Essani K
Department of Biological Sciences, Western Michigan University, Kalamazoo 49008, USA.
Microb Pathog. 1998 Jul;25(1):33-41. doi: 10.1006/mpat.1998.0213.
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.
痘病毒编码的毒力因子已被鉴定为从受感染宿主细胞分泌的蛋白质。其中一些分泌蛋白会阻碍宿主的免疫防御。我们之前已经证明，塔纳痘病毒（TPV）感染的细胞会分泌一种早期的38 kDa糖肽，它能与人（h）干扰素-γ、hIL-2和hIL-5结合。我们现在发现TPV感染细胞的上清液还有另外一种活性，即下调肿瘤坏死因子-α（TNF-α）诱导的细胞黏附分子基因表达。在模拟感染的细胞中未检测到这种活性。对原代人内皮细胞进行的酶联免疫吸附测定（ELISA）显示，正如预期的那样，在TNF-α或IL-1β处理后会诱导E-选择素、血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的表达。TPV感染细胞的上清液显著降低了TNF-α诱导的这些分子的表达，但对IL-1β诱导的表达没有影响。迁移率变动分析和Northern印迹分析进一步表明，TPV感染细胞的上清液抑制了TNF-α诱导的核转录因子-κB（NF-κB）的激活以及E-选择素、VCAM-1和ICAM-1基因的转录激活。基于TNF-α亲和层析，这种活性似乎与一种38 kDa糖肽有关。
