Cytomegalovirus infection decreases expression of thrombospondin-1 and-2 in cultured human retinal glial cells: Effects of antiviral agents
Cytomegalovirus infection decreases expression of thrombospondin-1 and-2 in cultured human retinal glial cells: Effects of antiviral agents
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DOI：
10.1086/315779
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发表时间：
2000-09-01
影响因子：
6.4
通讯作者：
Doerr, HW
中科院分区：
文献类型：
--
作者：
Cinatl, J;Bittoova, M;Doerr, HW
在成纤维细胞中，人巨细胞病毒（HCMV）感染抑制细胞外基质蛋白血小板反应蛋白-1和-2（TSP-1和TSP-2）的表达。这些作用可能依赖于HCMV立即早期（IE）基因的表达，这些基因被细胞转录因子NF-κ B激活。观察HCMV感染对人视网膜神经胶质细胞TSP-1和TSP-2表达的影响以及不同抗病毒药物预防这些细胞变化的能力。更昔洛韦仅抑制HCMV晚期抗原（LA）表达，而反义寡核苷酸ISIS 2922和肽SN 50（HCMV IE表达和NF-κ B活性的抑制剂）分别抑制IE和LA表达。ISIS 2922和SN 50，而不是更昔洛韦，阻止了TSP-1和TSP-2的下调。结果表明，HCMV诱导的视网膜胶质细胞中TSP-1和TSP-2的下调可通过抑制HCMV IE表达来防止。这些发现可能与HCMV视网膜炎的发病机制和治疗有关。
In fibroblasts, infection with human cytomegalovirus (HCMV) inhibits expression of the extracellular matrix proteins thrombospondin-1 and -2 (TSP-1 and TSP-2). These effects may depend on expression of HCMV immediate-early (IE) genes, which are activated by cellular transcription factor NF-kappa B. The influence of HCMV infection on TSP-I and TSP-2 expression and the ability of different antiviral drugs to prevent these cellular changes in permissive cultures of human retinal glial cells were observed. Ganciclovir inhibited only HCMV late antigen (LA) expression, whereas antisense oligonucleotide ISIS 2922 and peptide SN50, inhibitors of HCMV IE expression and NF-kappa B activity, respectively, inhibited both IE and LA expression. ISIS 2922 and SN50, but not ganciclovir, prevented down-modulation of TSP-1 and TSP-2. The results showed that HCMV-induced down-modulation of TSP-1 and TSP-2 in retinal glial cells is prevented by inhibition of HCMV IE expression. These findings may be relevant to pathogenesis and treatment of HCMV retinitis.