Delannoy A S, Hober D, Bouzidi A, Wattre P
Laboratoire de Virologie, Institut Gernez Rieux, Centre Hospitalier et Universitaire de Lille, France.
Microbiol Immunol. 1999;43(12):1087-96. doi: 10.1111/j.1348-0421.1999.tb03365.x.
The role of cytokines in the control of HCMV infection has been studied in THP-1 cells, a macrophage-like cell model and in MRC-5 cells. HCMV replication was studied by immune detection of viral immediate-early antigens (IEA) and virus yield was evaluated in MRC-5 cells by immunoperoxidase staining. Pretreatment of MRC-5 and phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells with IFN-alpha or IFN-gamma for 24 hr prior to the infection reduced the number of infected cells and virus yield. A synergistic anti-CMV activity in synthesis of early proteins was obtained with these cytokines in combination with TNF-alpha in differentiated THP-1 cells only. Treatment of HCMV-infected differentiated THP-1 cells or MRC-5 cells with IFN-alpha or IFN-gamma alone had no inhibitory effect on virus replication, however the virus yield was reduced with ganciclovir. A synergistic anti-CMV activity in virus yield was obtained only when infected differentiated THP-1 cells were treated with ganciclovir in combination with IFN-gamma. The current study shows that IFN-alpha and IFN-gamma can play a role in the reduction of HCMV replication in macrophage-like cells and in the efficiency of therapies with ganciclovir in this cell type and that the anti-CMV effect of cytokines may be different in fibroblasts and in macrophage-like cells.
细胞因子在控制人巨细胞病毒（HCMV）感染中的作用已在THP-1细胞（一种巨噬细胞样细胞模型）和MRC-5细胞中进行了研究。通过免疫检测病毒即刻早期抗原（IEA）来研究HCMV复制，并通过免疫过氧化物酶染色在MRC-5细胞中评估病毒产量。在感染前用IFN-α或IFN-γ对MRC-5细胞和佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）处理的THP-1细胞预处理24小时，可减少感染细胞的数量和病毒产量。仅在分化的THP-1细胞中，这些细胞因子与TNF-α联合使用时，在早期蛋白合成中获得了协同的抗CMV活性。单独用IFN-α或IFN-γ处理HCMV感染的分化THP-1细胞或MRC-5细胞对病毒复制没有抑制作用，然而用更昔洛韦可降低病毒产量。仅当用更昔洛韦与IFN-γ联合处理感染的分化THP-1细胞时，在病毒产量方面获得了协同的抗CMV活性。当前研究表明，IFN-α和IFN-γ在减少巨噬细胞样细胞中HCMV复制以及在这种细胞类型中使用更昔洛韦的治疗效率方面可发挥作用，并且细胞因子的抗CMV作用在成纤维细胞和巨噬细胞样细胞中可能有所不同。
